Affinage

TP53BP2

Apoptosis-stimulating of p53 protein 2 · UniProt Q13625

Length
1128 aa
Mass
125.6 kDa
Annotated
2026-06-10
100 papers in source corpus 50 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASPP2 (TP53BP2) is a multidomain scaffold protein that couples the p53 family to programmed cell death and links cell polarity, RAS signaling, and metabolic control to tumor suppression (PMID:8875926, PMID:14729977, PMID:23248303). Its C-terminal ankyrin repeats and SH3 domain dock onto the DNA-binding domains of p53, p63, and p73 — engaging the L2 and L3 loops of the p53 core in a mode that overlaps the DNA-binding surface, such that the six most frequent cancer-associated p53 mutations disrupt the interaction and ASPP2 binding is mutually exclusive with response-element DNA binding (PMID:8875926, PMID:16887812, PMID:18676979, PMID:22917970). Through this interface ASPP2 selectively stimulates transcription of pro-apoptotic targets (Bax, PUMA, PIG3) rather than cell-cycle arrest genes, and much of its p53-independent apoptotic output is relayed through p63/p73 (PMID:14729977). The same Ank-SH3 module binds Bcl-2 family proteins at the conserved BH4 motif and engages NF-κB p65/RelA, while a natively disordered N-terminal proline-rich domain folds back to autoinhibit Ank-SH3, gating partner access (PMID:8668206, PMID:18719108, PMID:18448430, PMID:23472201). ASPP2 activity is tuned by MAPK/ERK phosphorylation that enhances p53 binding upon RAS activation, by FIH-1 hydroxylation of Asn-986 that licenses Par-3 binding, and by proteasomal turnover through the E3 ligases Itch and Siah2 (PMID:24312625, PMID:23606740, PMID:25436413, PMID:23644657). Beyond apoptosis, ASPP2 acts at apical cell-cell junctions: it binds Par-3 to maintain epithelial and neuroepithelial polarity and scaffolds PP1 to dephosphorylate and activate junctional YAP/TAZ (PMID:20619750, PMID:20619648, PMID:21189257, PMID:25360797). Its N-terminal RAS-association domain binds Ras-GTP at the membrane, potentiating Raf/MEK/ERK signaling and oncogene-induced senescence and cooperating with oncogenic RAS to enhance p53-dependent apoptosis (PMID:23248303, PMID:23392125). ASPP2 further suppresses tumorigenic programs by restraining ΔNp63 via NF-κB, blocking β-catenin-driven ZEB1 to promote mesenchymal-to-epithelial transition, inhibiting autophagy initiation, and restricting nuclear SREBP-2 control of the mevalonate pathway (PMID:24127607, PMID:25344754, PMID:27929538, PMID:31685796). The H. pylori oncoprotein CagA exploits the disordered ASPP2 proline-rich region to form a high-affinity complex that subverts ASPP2 polarity and apoptotic functions (PMID:21562218, PMID:24474782, PMID:31964836).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1996 High

    Established the structural basis for how ASPP2 recognizes p53 and why the interaction is tumor-relevant, answering how a non-DNA-binding partner engages the p53 core.

    Evidence X-ray crystallography of the p53 core–53BP2 complex with cancer-mutant in vitro binding assays

    PMID:8875926

    Open questions at the time
    • Did not show whether binding occurs on or off DNA in cells
    • No functional transcriptional consequence quantified
  2. 1996 High

    Showed ASPP2 also binds Bcl-2 through the same Ank-SH3 domains and that Bcl-2 and p53 compete, raising the possibility of partner-switching control of apoptosis.

    Evidence Yeast two-hybrid, in vitro GST pull-down with competition assays, immunofluorescence, flow cytometry

    PMID:8668206

    Open questions at the time
    • Physiological relevance of competition not established in vivo
    • Cytoplasmic colocalization only partial
  3. 1998 Medium

    Resolved the puzzle that cytoplasmic ASPP2 still enhances p53 transcriptional output, framing it as a signal-transduction modulator rather than an obligatory nuclear cofactor.

    Evidence Immunofluorescence localization plus p53-dependent reporter and target-protein assays

    PMID:9748285

    Open questions at the time
    • Mechanism connecting cytoplasmic ASPP2 to nuclear p53 unresolved
    • Single-lab observation
  4. 1999 Medium

    Identified NF-κB p65/RelA as a direct ASPP2 partner that suppresses ASPP2-induced apoptosis and mapped apoptotic activity to the full-length protein.

    Evidence Yeast two-hybrid, in vitro and mammalian two-hybrid, GFP localization, transfection apoptosis assay

    PMID:10498867

    Open questions at the time
    • Domain of p65 binding not precisely mapped here
    • p53-dependence of the apoptotic effect not isolated
  5. 2000 High

    Placed ASPP2 in the DNA-damage response by showing UV induces its protein in a p53-independent manner while wild-type p53 suppresses it, defining a feedback relationship that lowers the apoptotic threshold.

    Evidence Western blot in defined-genotype lines, inducible expression, antisense knockdown, clonogenic and apoptosis assays

    PMID:11027272

    Open questions at the time
    • Mechanism of p53-mediated ASPP2 suppression not defined
    • Post-transcriptional vs transcriptional control unclear
  6. 2002 High

    Defined the central functional principle: ASPPs selectively drive apoptotic over arrest p53 targets and extend this to p63/p73, with p63/p73 carrying p53-independent apoptosis.

    Evidence Co-IP, in vitro binding, promoter-selective luciferase reporters, p63/p73 RNAi epistasis, apoptosis assays

    PMID:14729977

    Open questions at the time
    • Molecular basis of promoter selectivity not structurally explained
    • How ASPP2 distinguishes apoptotic from arrest promoters unknown
  7. 2003 Medium

    Connected ASPP2 to neddylation control by showing it binds APP-BP1 and inhibits NEDD8 conjugation to Cullin-1, with consequences for proliferation and neuronal apoptosis.

    Evidence Endogenous Co-IP, domain mapping, NEDD8 conjugation assay, proliferation and apoptosis assays

    PMID:12694406

    Open questions at the time
    • Integration with p53/apoptotic functions unclear
    • Single-lab finding
  8. 2004 Medium

    Defined gene architecture (53BP2S short and 53BP2L/ASPP2 long isoforms) by alternative splicing, providing the basis for isoform-specific functions.

    Evidence RT-PCR, genomic cloning, sequencing of TP53BP2 transcripts

    PMID:14766226

    Open questions at the time
    • Functional differences between isoforms not assessed here
  9. 2004 Medium

    Showed HCV core protein competes with p53 for ASPP2, an early example of viral subversion of ASPP2-enhanced apoptosis.

    Evidence Yeast two-hybrid, in vitro competition binding, apoptosis and reporter assays

    PMID:14985081

    Open questions at the time
    • Binding site on ASPP2 not mapped
    • In-cell relevance during infection not tested
  10. 2005 High

    Multiple studies defined ASPP2 regulatory inputs and outputs: E2F transcriptional induction in S-phase, proteasomal stability control, the mutually exclusive p53/DNA-binding mechanism, Mdm2/MdmX antagonism, and a mitochondrial apoptotic pathway.

    Evidence ChIP and promoter reporters; proteasome inhibition and ubiquitination assays; biophysical binding (SPR/ITC/anisotropy) with p53 mutant panels; mutant dissection; subcellular fractionation with caspase-9 assays

    PMID:15592436 PMID:15731768 PMID:15743414 PMID:15782125 PMID:16091363 PMID:16887812

    Open questions at the time
    • E3 ligase mediating ASPP2 ubiquitination not yet identified in this period
    • How cytoplasmic/mitochondrial ASPP2 ties to nuclear p53 transcription unresolved
  11. 2008 High

    Quantitative biophysics and NMR established the autoinhibitory architecture and binding thermodynamics: the disordered Pro domain competes with Ank-SH3 for partner peptides, and ASPP2 binds Bcl-2 family BH4 motifs and p53/p63/p73 DBDs at low-micromolar 1:1 stoichiometry, with ASPP2 uniquely binding PUMA DNA.

    Evidence CD, NMR, SEC, fluorescence anisotropy, peptide arrays, SPR, ITC, EMSA, homology modeling

    PMID:18448430 PMID:18676979 PMID:18719108

    Open questions at the time
    • Trigger that relieves intramolecular autoinhibition in cells not defined
    • Functional impact of PUMA-DNA binding on transcription unresolved
  12. 2008 Medium

    Identified DDA3 as a p53-target oncoprotein that binds ASPP2 and inhibits its stimulation of p53-mediated BAX activation without blocking ASPP2–p53 binding.

    Evidence Yeast two-hybrid, GST pull-down, colocalization, domain mapping, BAX reporter assay

    PMID:18793611

    Open questions at the time
    • Mechanism of inhibition without disrupting p53 binding unclear
    • Single-lab finding
  13. 2009 High

    Revealed a p53-independent role in epithelial/neuroepithelial polarity by showing ASPP2 binds Par-3 and maintains junctions, with loss causing neuroepithelial tumor-like phenotypes in vivo.

    Evidence In vivo mouse CNS loss-of-function, Co-IP, immunofluorescence

    PMID:20619750

    Open questions at the time
    • Biochemical determinants of the Par-3 interaction not mapped here
    • Link between polarity loss and tumorigenesis mechanistic at this stage
  14. 2010 Medium

    Extended the polarity role to epithelial cells and mechanistically linked ASPP2 to YAP/TAZ regulation, showing it scaffolds PP1 to dephosphorylate TAZ and facilitates the Par-3 apical complex.

    Evidence Co-IP, immunofluorescence, siRNA depletion, in vitro phosphatase assay, fractionation, reporter assays

    PMID:20619648 PMID:21189257

    Open questions at the time
    • How polarity and apoptotic functions are coordinated unclear
    • PP1 scaffolding stoichiometry not defined
  15. 2012 High

    Defined the N-terminal RAS-association function: ASPP2 binds Ras-GTP at the membrane, potentiates Raf/MEK/ERK signaling and oncogene-induced senescence, distinguishing the long isoform from senescence-incompetent 53BP2S.

    Evidence Ras-GTP pull-down, Co-IP, pERK Western, confocal colocalization, Raf dimerization, senescence assay, isoform comparison

    PMID:23248303

    Open questions at the time
    • How RAS engagement feeds back to p53/apoptosis not yet linked here
    • Structural basis of RA-domain–Ras binding not solved
  16. 2012 High

    Crystallography of the p73 DBD–ASPP2 Ank-SH3 complex showed conformational adaptation accommodates the divergent p73 L2 loop, explaining conserved binding across the p53 family.

    Evidence X-ray crystallography of free and ASPP2-bound p73 DBD

    PMID:22917970

    Open questions at the time
    • Affinity differences across family members not functionally resolved here
  17. 2013 High

    A cluster of studies defined ASPP2 post-translational and signaling regulation: FIH-1 hydroxylation of Asn-986 gating Par-3 binding, MAPK phosphorylation enhancing p53 binding upon RAS activation, NF-κB-mediated ΔNp63 repression as a tumor-suppressive axis, mapped competing autoinhibitory/partner sites on the SH3, Csk-dependent Src inactivation, Siah2-mediated hypoxic degradation, and RAS cooperation to enhance p53 apoptosis.

    Evidence MS PTM mapping with mutagenesis and Co-IP; in vitro kinase assays with phospho-mutants; Co-IP/ChIP and mouse genetic epistasis; biophysical competition; Csk RNAi epistasis with migration; LC-MS/MS, ubiquitination and 3D polarity assays; Ras-GTP pull-down with apoptosis reporters

    PMID:23392125 PMID:23472201 PMID:23606740 PMID:23644657 PMID:23671128 PMID:24127607 PMID:24312625

    Open questions at the time
    • Crosstalk between hydroxylation, phosphorylation, and degradation inputs not integrated
    • Stimulus-specific deployment of distinct ASPP2 functions unresolved
  18. 2014 High

    Defined the CagA–ASPP2 hijacking mechanism structurally and functionally, and expanded ASPP2 tumor-suppressive functions to MET, YAP/PP1 junctional scaffolding, autophagic apoptosis via CHOP-Bcl-2-Beclin-1, and Itch-mediated degradation antagonized by Yap1.

    Evidence 2.0 Å co-crystal with mutagenesis; Co-IP of ternary β-catenin/E-cadherin complex with in vivo MET/metastasis models; PP1–YAP scaffold Co-IP with in vivo colonic epithelium; CHOP RNAi pathway dissection; PPXY–WW ubiquitination and competition assays

    PMID:24474782 PMID:25032846 PMID:25344754 PMID:25360797 PMID:25436413

    Open questions at the time
    • Hierarchy among ASPP2 polarity, MET, and apoptotic outputs unclear
    • Whether these functions operate in the same cell context not established
  19. 2015 Medium

    Refined CagA binding to a distributed disordered ASPP2 region, defined ASPP2–Csk–Src–Snail suppression of HCC stemness, and identified an ASPP1/2–PP1α–C-Nap1 axis in centrosome linker reassembly.

    Evidence SEC-MALS/NMR/SPR/ITC/peptide arrays; Co-IP with Csk kinase and AP1/Snail reporters and stemness assays; Co-IP with phospho-C-Nap1 and centrosome imaging

    PMID:25660448 PMID:25963096 PMID:27473084

    Open questions at the time
    • Mitotic centrosome role not connected to apoptotic/polarity functions
    • Csk-stimulating mechanism not structurally defined
  20. 2017 Medium

    Showed ASPP2 suppresses TGF-β1-induced EMT by stabilizing Smad7 through inhibition of ITCH-mediated degradation, integrating ASPP2 into junctional and TGF-β anti-tumor control.

    Evidence Co-IP, Smad7 degradation assay, Smad2/3 Western, immunofluorescence, migration/invasion and in vivo dissemination

    PMID:28400336

    Open questions at the time
    • Relationship between ASPP2–ITCH stabilization of Smad7 and Itch-mediated ASPP2 degradation unclear
    • Single-lab finding
  21. 2019 Medium

    Linked ASPP2 to lipid metabolism by showing it restrains nuclear SREBP-2 control of the mevalonate pathway, and identified a dominant-negative splice isoform (ASPP2κ) that impairs p53 apoptosis and drives chromosomal instability.

    Evidence Nuclear Co-IP, ChIP/reporter, cholesterol measurement, xenograft and simvastatin rescue; isoform-specific KD/OE with CIN assays

    PMID:30952616 PMID:31685796

    Open questions at the time
    • Direct vs indirect SREBP-2 inhibition mechanism not fully resolved
    • Regulation of ASPP2κ splicing under stress not detailed
  22. 2020 Medium

    Defined CagA-driven PAR-complex remodeling in gastric organoids and a truncated ASPP2–PP1 actomyosin/YAP mechanism enabling E-cadherin-deficient epithelial survival in lobular carcinoma.

    Evidence Organoid infection with high-content imaging, EGFR-inhibitor and decoy-peptide rescue; mouse ILC model with PP1 domain mapping and YAP dissection

    PMID:31964836 PMID:32060147

    Open questions at the time
    • Generality of t-ASPP2 mechanism beyond ILC unclear
    • How truncation alters ASPP2 partner selection not detailed
  23. 2021 Medium

    Established autophagy/transcription control roles in viral and stress contexts: ASPP2 sequesters HSF1 to block ATG7 transcription and limit HBV-induced autophagy, and is itself an ATF4 transcriptional target driving inflammation and apoptosis during ischemia/reperfusion.

    Evidence Co-IP, fractionation and ChIP for HSF1–ATG7; ChIP of ATF4 on TP53BP2 promoter with overexpression and in vivo I/R models

    PMID:33751357 PMID:34085409

    Open questions at the time
    • Direct ASPP2 contact residues on HSF1 not mapped
    • Integration with NF-κB/Beclin-1 autophagy control unclear
  24. 2016 Medium

    Defined dual autophagy suppression: ASPP2 inhibits NF-κB-driven BECN1 transcription via an ASPP2–p65–IκBα complex and reshapes the PIK3C3–Beclin-1 complex to block autophagy initiation.

    Evidence Co-IP, IκBα phosphorylation assay, BECN1 promoter reporter, PIK3C3 complex pull-down, autophagic flux, xenograft

    PMID:27929538

    Open questions at the time
    • Balance between pro-autophagic (CHOP axis) and anti-autophagic ASPP2 effects unresolved
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ASPP2's distinct modular functions — p53-family apoptosis, RAS signaling, junctional polarity/YAP, autophagy and metabolic control — are coordinated and selectively deployed within a single cell remains unresolved.
  • No structure of full-length ASPP2 with multiple partners
  • Stimulus-to-function mapping incomplete
  • Role of low-confidence partners (Ddx42p, SOCS2 axis) not validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0098772 molecular function regulator activity 5 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 1
Localization
GO:0005829 cytosol 4 GO:0005886 plasma membrane 4 GO:0005634 nucleus 3 GO:0005739 mitochondrion 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 3
Partners
BCL2ITCHPARD3PPP1CARASRELATP53TP73
Complex memberships
ASPP2–PP1–YAP junctional polarity complexASPP2–p65/RelA–IκBα complexASPP2–β-catenin–E-cadherin complexPIK3C3–Beclin-1 complex

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Crystal structure of the p53 core domain bound to 53BP2 (ASPP2 C-terminal fragment) revealed that the SH3 domain of 53BP2 binds the L3 loop of p53 in a manner distinct from canonical SH3-polyproline complexes, and an ankyrin repeat binds the L2 loop of p53; the binding site overlaps the p53 DNA-binding surface and the six most frequent cancer-associated p53 mutations disrupt 53BP2 binding in vitro. X-ray crystallography (crystal structure of p53 core domain–53BP2 complex); in vitro binding assays with cancer-associated p53 mutants Science High 8875926
1996 53BP2/ASPP2 interacts with Bcl-2 via its ankyrin repeats and SH3 domain (same domains that mediate p53 binding); Bcl-2 and p53 compete for binding to 53BP2 in vitro; overexpressed 53BP2 partially colocalizes with Bcl-2 in the cytoplasm and increases the proportion of cells at G2/M. Yeast two-hybrid screen; in vitro GST pull-down with bacterially expressed proteins; competition binding assays; immunofluorescence colocalization; cell cycle analysis by flow cytometry Molecular and cellular biology High 8668206
1998 53BP2 localizes exclusively to the cytoplasm (not altered by co-expression of wild-type p53); despite this, both 53BP1 and 53BP2 enhance p53-mediated transcriptional activation in cell-based reporter assays, suggesting they function in signal transduction pathways to promote p53 activity without forming a concurrent DNA-binding complex with p53. Immunofluorescence subcellular localization; p53-dependent transcriptional reporter assays; Western blot for p53 target protein induction The Journal of biological chemistry Medium 9748285
1999 NF-κB p65 (RelA) subunit directly binds 53BP2/ASPP2 via yeast two-hybrid and in vitro pull-down; co-expression of p65 significantly inhibits 53BP2-induced apoptosis; full-length GFP-53BP2 localizes to perinuclear cytoplasmic puncta and induces apoptosis, whereas N-terminal or C-terminal fragments alone do not. Yeast two-hybrid; in vitro pull-down assay; mammalian two-hybrid assay; GFP fusion subcellular localization; apoptosis assay by transfection Oncogene Medium 10498867
2000 Endogenous 53BP2/ASPP2 protein levels increase following UV-irradiation-induced DNA damage in a p53-independent manner; conversely, wild-type (but not mutant) p53 suppresses 53BP2 steady-state protein levels; conditional expression of 53BP2 lowers the apoptotic threshold after UV irradiation, and antisense attenuation of 53BP2 induction enhances clonogenic survival. Western blot of endogenous protein in cell lines with defined p53 genotypes; tetracycline-regulated p53 expression system; ecdysone-regulated 53BP2 stable cell lines; antisense oligonucleotide knockdown; clonogenic survival assay; apoptosis assay Molecular and cellular biology High 11027272
2002 ASPP1 and ASPP2 selectively stimulate the apoptotic transcriptional function of p53 (activating Bax, PIG3, PUMA promoters) but not cell-cycle arrest targets (mdm2, p21); they also bind p63 and p73 in vitro and in vivo and stimulate their apoptotic function; RNAi depletion of endogenous p63/p73 demonstrated that the p53-independent apoptotic activity of ASPP1/ASPP2 is mainly mediated by p63/p73. Co-immunoprecipitation (in vivo); in vitro binding; luciferase reporter assays on apoptotic vs. cell-cycle promoters; RNA interference knockdown of p63/p73; apoptosis assays Molecular and cellular biology High 14729977
2003 ASPP2 specifically interacts with APP-BP1 (the NEDD8-activating enzyme subunit) in non-transfected cells through the N-terminal domain ASPP2(332–483); ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to Cullin-1, reduces APP-BP1-induced cell proliferation, and blocks APP-BP1-triggered apoptosis in primary neurons; ASPP2 also activates NF-κB transcriptional activity. Co-immunoprecipitation from non-transfected cells; domain mapping; NEDD8 conjugation assay (in vitro/cellular); cell proliferation and neuronal apoptosis assays Journal of neurochemistry Medium 12694406
2004 Hepatitis C virus core protein interacts with 53BP2/ASPP2 in a yeast two-hybrid assay; the core protein competes with p53 for binding to ASPP2 in vitro and, when co-expressed, inhibits ASPP2-enhanced p53-mediated apoptosis without affecting p53 transcriptional activity on Bax or p21 promoters. Yeast two-hybrid; in vitro competition binding assay; apoptosis assay; reporter assay Biochemical and biophysical research communications Medium 14985081
2004 The TP53BP2 gene encodes two protein isoforms—53BP2S (short, 1005 aa) and 53BP2L/ASPP2 (long, 1128 aa, with an additional N-terminal 123 aa encoded by exon 3)—generated by alternative splicing. RT-PCR and genomic cloning of TP53BP2 transcripts; sequencing Biochemical and biophysical research communications Medium 14766226
2005 ASPP2/53BP2L is a transcriptional target of E2F: E2F-1, -2, and -3 bind the endogenous ASPP2 promoter (demonstrated by ChIP), and ectopic E2F-1 increases endogenous ASPP2 mRNA and protein; ASPP2 expression is maximal in early S-phase. Chromatin immunoprecipitation (ChIP); luciferase promoter-reporter assays with E2F binding site mutants; Western blot and RT-PCR of endogenous protein after E2F-1 induction; cell-cycle-staged expression analysis Cell death and differentiation High 15592436 15731768
2005 ASPP2/53BP2L protein is subject to proteasomal degradation; proteasomal inhibitors (including bortezomib) and anthracycline-based chemotherapy increase ASPP2 protein but not mRNA levels by stabilizing the protein; the central region of ASPP2 is ubiquitinated; siRNA knockdown of ASPP2 attenuates bortezomib-induced apoptosis, particularly in p53 wild-type cells. Proteasome inhibitor treatment; cycloheximide chase (protein half-life); ubiquitination assay; siRNA knockdown; apoptosis assay The Journal of biological chemistry Medium 16091363
2005 53BP2 binding to p53 and DNA binding are mutually exclusive (no ternary complex detected for GADD45, p21, Bax, or PIG3 response elements); multiple oncogenic p53 mutations (R181E, G245S, R249S, R273H) differentially affect DNA and 53BP2 binding. Biophysical binding assays (fluorescence anisotropy, isothermal titration calorimetry, SPR); competition experiments with DNA response elements and recombinant proteins; p53 mutant panel The Journal of biological chemistry High 16887812
2005 Mdm2 and MdmX prevent ASPP1/ASPP2 from stimulating the apoptotic function of p53 by binding and inhibiting the transcriptional activity of p53, without targeting p53 for degradation; both the DNA-binding and transactivation functions of p53 are required for ASPP1/ASPP2 stimulation. p53/mdm2 mutant panel; transcriptional reporter assays; co-immunoprecipitation; Western blot for p53 stability Oncogene Medium 15782125
2005 53BP2/ASPP2 induces apoptosis via the mitochondrial death pathway: it localizes to mitochondria, causes depression of mitochondrial transmembrane potential (ΔΨm), and activates caspase-9 leading to PARP cleavage. Subcellular fractionation; mitochondrial membrane potential assay (JC-1); caspase-9 activity assay; annexin V staining; PARP cleavage Western blot Genes to cells Medium 15743414
2008 ASPP2 C-terminal ankyrin repeats and SH3 domain (ASPP2 Ank-SH3) mediate interaction with Bcl-2 family members (Bcl-2, Bcl-xL, Bcl-w) at two sites: the conserved BH4 motif and a proapoptotic regulator-binding site; within Bcl-2, binding to the BH4 domain is tightest; based on docking analysis ASPP2 is proposed to inhibit Bcl-2 function by occupying functional sites. Peptide array screening; surface plasmon resonance (SPR); isothermal titration calorimetry (ITC); computational docking; sequence alignment and peptide mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 18719108
2008 The C-termini of ASPP1 and ASPP2 directly bind the DNA-binding domains of p53, p63, and p73 with dissociation constants in the low micromolar range in a 1:1 stoichiometry; tri-complex formation between ASPPs, p53 family members, and PUMA/Bax DNA is mutually exclusive; uniquely, ASPP2 (but not ASPP1) forms a complex with PUMA and displaces p53 and p73. Surface plasmon resonance; isothermal titration calorimetry; EMSA (electrophoretic mobility shift assay); structure-based homology modelling Nucleic acids research High 18676979
2008 The proline-rich domain of ASPP2 is natively unfolded and forms an intramolecular autoinhibitory interaction with its own Ank-SH3 domains, competing with intermolecular partner binding; ASPP2 Ank-SH3 (not the Pro domain) mediates interactions with partner-derived peptides; the presence of the Pro domain inhibits interactions mediated by Ank-SH3. CD spectroscopy; NMR; size exclusion chromatography; fluorescence anisotropy; peptide array screening; GST pull-down The Journal of biological chemistry High 18448430
2009 ASPP2 binds Par-3 and controls its apical/junctional localization in neural progenitors; junctional localization of ASPP2 and Par-3 is interdependent; loss of ASPP2 in vivo disrupts tight/adherens junctions, impairs interkinetic nuclear migration, and causes neuroblastic rosette formation resembling primitive neuroepithelial tumors. In vivo mouse CNS development model (conditional knockdown/KO); co-immunoprecipitation; immunofluorescence localization; ASPP2 heterozygous and homozygous loss-of-function analysis Developmental cell High 20619750
2010 ASPP2 interacts and colocalizes with PAR-3 at apical cell-cell junctions in polarized epithelial cells; depletion of ASPP2 causes polarity defects (tight junction formation, apical domain development) and mislocalization of PAR-3; disruption of the ASPP2–PAR-3 interaction causes the same polarity defects. Co-immunoprecipitation; immunofluorescence colocalization; siRNA depletion; domain-interaction mapping Current biology High 20619648
2010 PP1A dephosphorylates TAZ at Ser-89 and Ser-311, promotes TAZ nuclear translocation, and stabilizes TAZ by disrupting SCF E3 ubiquitin ligase binding; ASPP2 facilitates the interaction between TAZ and PP1, thereby promoting TAZ dephosphorylation and TAZ-dependent gene expression. In vitro phosphatase assay; co-immunoprecipitation; phospho-specific antibody Western blot; nuclear/cytoplasmic fractionation; gene reporter assay The Journal of biological chemistry Medium 21189257
2011 H. pylori CagA associates with ASPP2 upon translocation into host cells; this CagA–ASPP2 interaction recruits p53 into the complex, inhibits p53 apoptotic function, and leads to enhanced p53 degradation in an ASPP2-dependent manner; CagA-infected cells show increased resistance to doxorubicin-induced apoptosis requiring ASPP2. Co-immunoprecipitation from infected cells; apoptosis assay with doxorubicin; siRNA depletion of ASPP2; Western blot for p53 levels Proceedings of the National Academy of Sciences of the United States of America High 21562218
2012 ASPP2 N-terminal RAS-association domain binds Ras-GTP at the plasma membrane and stimulates Ras-induced Raf/MEK/ERK signaling by promoting Ras-GTP loading, B-Raf/C-Raf dimerization, and C-Raf phosphorylation; decreased ASPP2 attenuates H-RasV12-induced senescence in normal human fibroblasts and keratinocytes; the short isoform BBP/53BP2S, lacking the N-terminus, fails to bind Ras-GTP or stimulate ERK. Ras-GTP pull-down; co-immunoprecipitation (Ras-GTP/ASPP2); pERK Western blot; plasma membrane colocalization by confocal microscopy; Raf dimerization assay; senescence assay (β-galactosidase); isoform comparison (53BP2S vs ASPP2) Proceedings of the National Academy of Sciences of the United States of America High 23248303
2013 ASPP1 and ASPP2 preferentially bind active (GTP-loaded) RAS via their N-terminal RAS-association domains; ASPP2 co-localizes with RAS at the cellular membrane and contributes to RAS membrane localization; in cancer cells, ASPP1/ASPP2 cooperate with oncogenic RAS to enhance p53 transcriptional apoptotic function. Pull-down with Ras-GTP (GTP-agarose); co-immunoprecipitation; confocal colocalization; luciferase reporter for p53 transcriptional targets; apoptosis assay Cell death and differentiation Medium 23392125
2013 FIH-1 (factor inhibiting HIF-1) hydroxylates ASPP2 at asparagine-986 within the ankyrin repeat domain; this hydroxylation is required for Par-3 binding to ASPP2—FIH-1 depletion impairs Par-3–ASPP2 interaction and causes relocation of ASPP2 from cell-cell contacts to the cytosol—without affecting p53 binding, apoptosis, or proliferation. Mass spectrometry identification of hydroxylation site; site-directed mutagenesis; co-immunoprecipitation; immunofluorescence localization; siRNA depletion of FIH-1; FIH-1 inhibitor (DMOG) Journal of cell science High 23606740
2013 ASPP2 inhibits ΔNp63 expression through its ability to bind IκB and enhance nuclear RelA/p65 (NF-κB), which mediates transcriptional repression of p63; heterozygosity of p63 (but not p53) prevents squamous cell carcinoma development in ASPP2-haploinsufficient mice. Co-immunoprecipitation (ASPP2–IκB interaction); nuclear fractionation; ChIP for RelA/p65 on p63 promoter; genetic epistasis (p63+/−; p53+/− crosses with ASPP2Δexon3/+ mice); tumor incidence analysis Proceedings of the National Academy of Sciences of the United States of America High 24127607
2013 ASPP2 intramolecular autoinhibitory interaction: the disordered proline-rich domain of ASPP2 competes with p53 core domain for binding the n-src loop of the ASPP2 SH3 domain; p53 core domain and NFκB (residues 303–332) bind partially overlapping sites on the ASPP2 SH3 RT loop; Bcl-2 binds ASPP2 at sites largely distinct from p53/NFκB. Fluorescence anisotropy competition experiments; peptide-based binding studies; recombinant protein assays PloS one Medium 23472201
2013 ASPP2 is a novel substrate of MAPK (ERK); MAPK phosphorylation of ASPP2 is required for RAS-induced increased binding to p53 and enhanced transactivation of pro-apoptotic genes; a phosphorylation-deficient ASPP2 mutant shows reduced p53 binding and fails to enhance apoptosis. In vitro MAPK kinase assay; phosphorylation-deficient ASPP2 mutant; co-immunoprecipitation of ASPP2–p53; luciferase reporter assay; apoptosis assay PloS one Medium 24312625
2013 ASPP2 attenuates Src kinase activation in a Csk (C-terminal Src kinase)-dependent manner; ASPP2 (but not ASPP1) transfection decreases Src-pY416 phosphorylation; this ASPP2-mediated Src inactivation reduces cell migration. Transfection of ASPP2 vs ASPP1; Western blot for Src-pY416; Csk siRNA epistasis; wound-healing/migration assay Carcinogenesis Medium 23671128
2013 DDA3 (a p53 target oncoprotein) binds ASPP2 via its residues 118–241 to both N- and C-terminal regions of ASPP2; DDA3 dose-dependently inhibits ASPP2-stimulated p53-mediated BAX promoter activation without interfering with ASPP2–p53 binding. Yeast two-hybrid screen; GST pull-down; immunofluorescence colocalization; domain mapping; luciferase BAX promoter reporter assay Biochemical and biophysical research communications Medium 18793611
2014 Crystal structure (2.0 Å) of the N-terminal CagA subdomain bound to a 7-kDa proline-rich sequence of ASPP2: CagA forms a three-helix bundle with a deep binding cleft for a 20-aa conserved ASPP2 peptide that adopts an extended helix; structure-based loss-of-contact mutations in either CagA or ASPP2 disrupt the interaction in vitro and in vivo and alter ASPP2 function. X-ray crystallography (2.0 Å co-crystal); yeast two-hybrid domain delineation; in vitro biochemical binding confirmation; structure-based mutagenesis; functional cell-based assays Proceedings of the National Academy of Sciences of the United States of America High 24474782
2014 ASPP2 induces mesenchymal-to-epithelial transition (MET) via its PAR3-binding N-terminus (independently of p53 binding); mechanistically, ASPP2 prevents β-catenin from transactivating ZEB1 by (i) forming an ASPP2–β-catenin–E-cadherin ternary complex and (ii) inhibiting N-terminal phosphorylation of β-catenin to stabilize the β-catenin–E-cadherin complex; ASPP2 limits oncogenic RAS pro-invasive effects and inhibits tumor metastasis in vivo. Co-immunoprecipitation (ASPP2–β-catenin–E-cadherin ternary complex); domain-mapping (N-terminus vs. p53-binding domain); β-catenin phosphorylation assay; in vivo mouse kidney MET model; in vivo metastasis assay Nature cell biology High 25344754
2014 ASPP2 forms an apical-lateral polarity complex at tight junctions acting as a scaffold for PP1 and junctional YAP via dedicated binding domains; ASPP2 directly induces dephosphorylation and activation of junctional YAP; this mechanism controls YAP function in polarized epithelial cells and in the murine colonic epithelium in vivo. Co-immunoprecipitation (ASPP2–PP1–YAP complex); domain mapping; phospho-YAP Western blot; siRNA depletion; in vivo murine colonic epithelium analysis PloS one Medium 25360797
2014 ASPP2 induces autophagic apoptosis in hepatoma cells through p53/p73-independent CHOP expression; CHOP decreases Bcl-2 expression, releasing Beclin-1 from Bcl-2–Beclin-1 complexes to initiate autophagy; ASPP2 also induces DRAM expression; CHOP promotes nuclear translocation of Bcl-2 where it is sequestered in ASPP2–Bcl-2 nuclear complexes, preventing Bcl-2 return to the cytoplasm. Western blot; co-immunoprecipitation (ASPP2–Bcl-2); siRNA knockdown of CHOP; adenoviral ASPP2 overexpression; autophagy and apoptosis assays; nuclear/cytoplasmic fractionation Cell death & disease Medium 25032846
2014 The E3 ubiquitin ligase Itch mediates ASPP2 degradation and ubiquitination via interaction of the ASPP2 PPXY motif with Itch WW domains; Yap1 competes with Itch for binding to ASPP2 and prevents Itch-mediated ASPP2 degradation, indicating antagonistic regulation of ASPP2 protein stability. Co-immunoprecipitation; ubiquitination assay in vivo; domain mapping (PPXY–WW interaction); competition binding assay; protein stability (CHX chase) FEBS letters Medium 25436413
2013 The ubiquitin E3 ligase Siah2 interacts with ASPP2 and ASPP1 under hypoxic conditions and targets ASPP2 for ubiquitination and proteasomal degradation via degron motifs in ASPP2; Siah2 inhibition increases ASPP2 levels and enhances tight junction integrity and polarity in 3D organotypic culture; hypoxia-induced Siah2 upregulation decreases ASPP2 levels and impairs polarity. LC-MS/MS identification of Siah2–ASPP2 interaction; co-immunoprecipitation; ubiquitination assay; degron mutant mapping; 3D organotypic culture; siRNA depletion; polarity assays Oncogene Medium 23644657
2015 ASPP2 physically interacts with C-terminal Src kinase (CSK) and stimulates its kinase activity, leading to Src inactivation, AP1-mediated downregulation of Snail expression, and suppression of HCC stemness; pharmacological inhibition of Src attenuates ASPP2-deficiency effects. Co-immunoprecipitation (ASPP2–CSK); CSK kinase activity assay; Src phosphorylation Western blot; AP1/Snail reporter; tumor sphere formation; side-population assay; Src inhibitor rescue Tumour biology Medium 27473084
2015 An intrinsically disordered region of ASPP2 (residues 448–692) that is unstructured in solution binds the N-terminal domain of CagA; peptide array mapping identified multiple distributed interaction sites throughout ASPP2 for CagA, extending beyond the crystallographically resolved fragment. SEC-MALS; circular dichroism; NMR; surface plasmon resonance; isothermal titration calorimetry; peptide array mapping Biochemistry High 25963096
2015 ASPP1 and ASPP2 interact with centrosome linker protein C-Nap1; co-depletion of ASPP1/2 inhibits C-Nap1 re-association with centrosomes at mitotic exit and impairs centrosome linker reassembly; ASPP1/2 facilitate PP1α–C-Nap1 interaction and antagonize NEK2A-mediated C-Nap1 Ser2417/2421 phosphorylation in a PP1-dependent manner. Co-immunoprecipitation (ASPP2–C-Nap1, ASPP2–PP1α); siRNA co-depletion; phospho-C-Nap1 (Ser2417/2421) Western blot; centrosome immunofluorescence; NEK2A kinase assay Biochemical and biophysical research communications Medium 25660448
2012 Crystal structure of the p73 DNA-binding domain (DBD) bound to ASPP2 ankyrin repeat and SH3 domains solved at high resolution; p73 DBD exhibits a divergent L2 loop (two-residue insertion that repacks the p53 R175 hotspot equivalent); ASPP2 binding is preserved via conformational adaptation in both the ankyrin repeat and SH3 domains. X-ray crystallography (high-resolution crystal structures of free p73 DBD and p73 DBD–ASPP2 Ank-SH3 complex) Journal of molecular biology High 22917970
2017 ASPP2 suppresses TGF-β1-induced EMT in gastric cancer cells by interacting with E3 ubiquitin ligase ITCH and inhibiting ITCH-mediated degradation of Smad7 (a negative regulator of TGF-β1–Smad2/3 signaling); ASPP2 promotes PAR3 recruitment to cell-cell junctions. Co-immunoprecipitation (ASPP2–ITCH); Smad7 degradation assay; TGF-β1–Smad2/3 signaling Western blot; immunofluorescence (PAR3 junctional localization); migration/invasion assay; in vivo peritoneal dissemination model Cancer letters Medium 28400336
2019 ASPP2 interacts with SREBP-2 in the nucleus and restricts SREBP-2 transcriptional activity on mevalonate pathway target genes (including HMGCR); ASPP2 depletion increases cholesterol levels and tumor-initiating capability; simvastatin rescues ASPP2-depletion-induced phenotypes. Co-immunoprecipitation (ASPP2–SREBP-2 nuclear); ChIP/reporter assay for SREBP-2 targets; cholesterol measurement; gene expression profiling; xenograft model; simvastatin pharmacological rescue Cell death & disease Medium 31685796
2016 ASPP2 inhibits NF-κB–induced transcription of BECN1 (Beclin-1) directly via an ASPP2–p65/RelA–IκBα complex that inhibits IκBα phosphorylation and p65 nuclear translocation; ASPP2 also binds BECN1 and reshapes the PIK3C3 complex (decreasing PIK3C3–UVRAG interaction, increasing Rubicon binding), thereby inhibiting autophagy initiation. Co-immunoprecipitation (ASPP2–p65–IκBα complex; ASPP2–BECN1); IκBα phosphorylation assay; BECN1 promoter-reporter assay; PIK3C3 complex pull-down; autophagic flux assay; xenograft model Cell death & disease Medium 27929538
2020 CagA–ASPP2 interaction promotes remodeling of the PAR polarity complex and loss of cell polarity in H. pylori-infected gastric epithelial cells; blockade of ASPP2 signaling by EGFR inhibitors or a CagA-binding ASPP2 peptide prevents polarity loss and decreases H. pylori survival in infected gastric organoids. Gastric organoid infection model; high-content imaging screen; co-immunoprecipitation/proximity ligation; EGFR inhibitor treatment; synthetic ASPP2 decoy peptide Proceedings of the National Academy of Sciences of the United States of America Medium 31964836
2020 Truncated ASPP2 (t-ASPP2, N-terminal truncation) induces actomyosin relaxation via interaction with PP1 to enable survival of E-cadherin-deficient mammary epithelial cells on stiff matrices (required for ILC initiation); separately, t-ASPP2-induced YAP activation (not actomyosin relaxation) contributes to tumor growth and progression. Mouse ILC model with E-cadherin loss; actomyosin tension assay; PP1 interaction domain mapping; YAP activity assay; conditional mouse genetics (PTEN loss) Cancer research Medium 32060147
2019 An alternatively spliced ASPP2 isoform, ASPP2κ (exon skipping generating truncated C-terminus lacking p53-binding sites), acts as a dominant-negative variant impairing TP53-dependent apoptosis induction; ASPP2κ expression causes perturbed proliferation, impaired apoptosis, mitotic failure, and chromosomal instability; its expression is stress-inducible. mRNA splice variant screening; isoform-specific PCR and epitope-specific antibody generation; forced expression and isoform-specific RNAi in cell models; apoptosis, proliferation, and chromosomal instability assays EBioMedicine Medium 30952616
2021 ASPP2 binds HSF1 in the cytoplasm of HBV-infected cells, preventing HSF1 nuclear translocation and thereby inhibiting transcriptional activation of ATG7; by suppressing ATG7 expression, ASPP2 reduces HBV-induced hepatocyte autophagy and inhibits HBV replication. Co-immunoprecipitation (ASPP2–HSF1); nuclear/cytoplasmic fractionation; ChIP for HSF1 on ATG7 promoter; Western blot for ATG7; autophagic flux assay; HBV replication assay Journal of cellular and molecular medicine Medium 34085409
2021 ATF4 transcription factor binds the TP53BP2 promoter (ChIP-validated) and drives TP53BP2 expression during ischemia/reperfusion stress; TP53BP2 overexpression promotes inflammation and apoptosis in hepatocytes, and sufentanil protection is mediated by suppression of ATF4-driven TP53BP2 induction. ChIP assay (ATF4 on TP53BP2 promoter); TP53BP2 overexpression in H/R cell model; Western blot; ELISA for inflammatory markers; in vivo rat I/R model Inflammation Medium 33751357
2009 DEAD-box protein Ddx42p physically interacts with ASPP2 via the Ddx42p C-terminal region and ASPP2 mid-N-terminal + Ank-SH3 domains; Ddx42p overexpression interferes with ASPP2-induced apoptosis; elevated Ddx42p shifts ASPP2 localization from nucleus+cytoplasm to predominantly cytoplasm. Co-immunoprecipitation; domain mapping; apoptosis assay with Ddx42p overexpression/knockdown; immunofluorescence localization Oncogene Low 19377511
2023 TP53BP2 downregulates SOCS2 expression, thereby facilitating JAK/STAT signaling and enhancing the anti-HBV effect of IFN-α in hepatocytes. In vitro and in vivo experiments; SOCS2 expression measurement upon TP53BP2 loss/gain; JAK/STAT pathway readouts; antiviral assay with IFN-α Journal of hepatology Low 37858684

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Structure of the p53 tumor suppressor bound to the ankyrin and SH3 domains of 53BP2. Science (New York, N.Y.) 428 8875926
2004 ASPP1 and ASPP2: common activators of p53 family members. Molecular and cellular biology 202 14729977
2011 Helicobacter pylori cytotoxin-associated gene A (CagA) subverts the apoptosis-stimulating protein of p53 (ASPP2) tumor suppressor pathway of the host. Proceedings of the National Academy of Sciences of the United States of America 187 21562218
1998 Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2. The Journal of biological chemistry 176 9748285
1996 The p53-binding protein 53BP2 also interacts with Bc12 and impedes cell cycle progression at G2/M. Molecular and cellular biology 143 8668206
2014 ASPP2 controls epithelial plasticity and inhibits metastasis through β-catenin-dependent regulation of ZEB1. Nature cell biology 128 25344754
2010 PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ. The Journal of biological chemistry 117 21189257
1999 NF-kappaB subunit p65 binds to 53BP2 and inhibits cell death induced by 53BP2. Oncogene 102 10498867
2010 ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Developmental cell 97 20619750
2010 Epigenetic silence of ankyrin-repeat-containing, SH3-domain-containing, and proline-rich-region- containing protein 1 (ASPP1) and ASPP2 genes promotes tumor growth in hepatitis B virus-positive hepatocellular carcinoma. Hepatology (Baltimore, Md.) 95 20034025
2014 CHOP mediates ASPP2-induced autophagic apoptosis in hepatoma cells by releasing Beclin-1 from Bcl-2 and inducing nuclear translocation of Bcl-2. Cell death & disease 88 25032846
2010 ASPP2 regulates epithelial cell polarity through the PAR complex. Current biology : CB 58 20619648
1994 Distinct residues of human p53 implicated in binding to DNA, simian virus 40 large T antigen, 53BP1, and 53BP2. Molecular and cellular biology 57 7969167
2013 ASPP1 and ASPP2 bind active RAS, potentiate RAS signalling and enhance p53 activity in cancer cells. Cell death and differentiation 51 23392125
2020 CagA-ASPP2 complex mediates loss of cell polarity and favors H. pylori colonization of human gastric organoids. Proceedings of the National Academy of Sciences of the United States of America 50 31964836
2014 Structure of the Helicobacter pylori CagA oncoprotein bound to the human tumor suppressor ASPP2. Proceedings of the National Academy of Sciences of the United States of America 50 24474782
2005 Apoptosis-stimulating protein of p53-2 (ASPP2/53BP2L) is an E2F target gene. Cell death and differentiation 50 15592436
2012 N terminus of ASPP2 binds to Ras and enhances Ras/Raf/MEK/ERK activation to promote oncogene-induced senescence. Proceedings of the National Academy of Sciences of the United States of America 48 23248303
2005 ASPP1 and ASPP2 are new transcriptional targets of E2F. Cell death and differentiation 47 15731768
2002 Apoptosis stimulating protein of p53 (ASPP2) expression differs in diffuse large B-cell and follicular center lymphoma: correlation with clinical outcome. Leukemia & lymphoma 46 12613517
2013 Factor inhibiting HIF-1 (FIH-1) modulates protein interactions of apoptosis-stimulating p53 binding protein 2 (ASPP2). Journal of cell science 45 23606740
2008 Molecular interactions of ASPP1 and ASPP2 with the p53 protein family and the apoptotic promoters PUMA and Bax. Nucleic acids research 45 18676979
2015 Downregulation of ASPP2 in pancreatic cancer cells contributes to increased resistance to gemcitabine through autophagy activation. Molecular cancer 44 26438046
2009 Apoptosis-stimulating protein of p53 (ASPP2) heterozygous mice are tumor-prone and have attenuated cellular damage-response thresholds. Proceedings of the National Academy of Sciences of the United States of America 44 19251665
2000 Aberrant overexpression of 53BP2 mRNA in lung cancer cell lines. FEBS letters 44 10631318
2016 Upregulation of MiR-205 under hypoxia promotes epithelial-mesenchymal transition by targeting ASPP2. Cell death & disease 42 27929537
2008 Molecular basis of the interaction between the antiapoptotic Bcl-2 family proteins and the proapoptotic protein ASPP2. Proceedings of the National Academy of Sciences of the United States of America 42 18719108
2013 ASPP2 suppresses squamous cell carcinoma via RelA/p65-mediated repression of p63. Proceedings of the National Academy of Sciences of the United States of America 41 24127607
2006 Effects of oncogenic mutations and DNA response elements on the binding of p53 to p53-binding protein 2 (53BP2). The Journal of biological chemistry 41 16887812
2016 Downregulation of ASPP2 improves hepatocellular carcinoma cells survival via promoting BECN1-dependent autophagy initiation. Cell death & disease 38 27929538
2008 The structure and interactions of the proline-rich domain of ASPP2. The Journal of biological chemistry 36 18448430
2000 Proapoptotic p53-interacting protein 53BP2 is induced by UV irradiation but suppressed by p53. Molecular and cellular biology 34 11027272
2014 ASPP2 enhances oxaliplatin (L-OHP)-induced colorectal cancer cell apoptosis in a p53-independent manner by inhibiting cell autophagy. Journal of cellular and molecular medicine 32 25534115
2003 ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to cullin-1 and decreases APP-BP1-induced cell proliferation and neuronal apoptosis. Journal of neurochemistry 32 12694406
2014 ASPP2 links the apical lateral polarity complex to the regulation of YAP activity in epithelial cells. PloS one 31 25360797
2017 ASPP2 suppresses invasion and TGF-β1-induced epithelial-mesenchymal transition by inhibiting Smad7 degradation mediated by E3 ubiquitin ligase ITCH in gastric cancer. Cancer letters 30 28400336
2018 Structural-dynamic insights into the H. pylori cytotoxin-associated gene A (CagA) and its abrogation to interact with the tumor suppressor protein ASPP2 using decoy peptides. Journal of biomolecular structure & dynamics 29 30328798
2014 STAT1-induced ASPP2 transcription identifies a link between neuroinflammation, cell polarity, and tumor suppression. Proceedings of the National Academy of Sciences of the United States of America 28 24958857
2019 ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma. Cell death & disease 27 31685796
2015 miR-548d-3p/TP53BP2 axis regulates the proliferation and apoptosis of breast cancer cells. Cancer medicine 27 26663100
2005 53BP2 induces apoptosis through the mitochondrial death pathway. Genes to cells : devoted to molecular & cellular mechanisms 27 15743414
2004 Expression of 53BP2 and ASPP2 proteins from TP53BP2 gene by alternative splicing. Biochemical and biophysical research communications 27 14766226
2014 ASPP2 attenuates triglycerides to protect against hepatocyte injury by reducing autophagy in a cell and mouse model of non-alcoholic fatty liver disease. Journal of cellular and molecular medicine 26 25256142
2004 Hepatitis C virus core protein interacts with p53-binding protein, 53BP2/Bbp/ASPP2, and inhibits p53-mediated apoptosis. Biochemical and biophysical research communications 26 14985081
2001 p53-interacting protein 53BP2 inhibits clonogenic survival and sensitizes cells to doxorubicin but not paclitaxel-induced apoptosis. Oncogene 26 11420684
2015 Nuclear EGFR impairs ASPP2-p53 complex-induced apoptosis by inducing SOS1 expression in hepatocellular carcinoma. Oncotarget 25 25980493
2005 Control of ASPP2/(53BP2L) protein levels by proteasomal degradation modulates p53 apoptotic function. The Journal of biological chemistry 25 16091363
2018 Downregulation of ASPP2 promotes gallbladder cancer metastasis and macrophage recruitment via aPKC-ι/GLI1 pathway. Cell death & disease 24 30389910
2023 Higher TP53BP2 expression is associated with HBsAg loss in peginterferon-α-treated patients with chronic hepatitis B. Journal of hepatology 23 37858684
2009 New insights into the expanding complexity of the tumor suppressor ASPP2. Cell cycle (Georgetown, Tex.) 23 19657229
2006 ASPP2: a gene that controls life and death in vivo. Cell cycle (Georgetown, Tex.) 23 16969108
2023 ASPP2 suppresses tumour growth and stemness characteristics in HCC by inhibiting Warburg effect via WNT/β-catenin/HK2 axis. Journal of cellular and molecular medicine 22 36752127
2013 Downregulation of ASPP2 in choriocarcinoma contributes to increased migratory potential through Src signaling pathway activation. Carcinogenesis 22 23671128
2021 Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression. Inflammation 21 33751357
2018 Silencing of ASPP2 promotes the proliferation, migration and invasion of triple-negative breast cancer cells via the PI3K/AKT pathway. International journal of oncology 21 29568874
2013 Siah2 regulates tight junction integrity and cell polarity through control of ASPP2 stability. Oncogene 21 23644657
2009 The DEAD box protein Ddx42p modulates the function of ASPP2, a stimulator of apoptosis. Oncogene 21 19377511
2009 A model for the interaction between NF-kappa-B and ASPP2 suggests an I-kappa-B-like binding mechanism. Proteins 18 19507243
2012 Structural basis for ASPP2 recognition by the tumor suppressor p73. Journal of molecular biology 17 22917970
2020 Mir-30b-5p Promotes Proliferation, Migration, and Invasion of Breast Cancer Cells via Targeting ASPP2. BioMed research international 16 32420372
2017 ASPP2 Inhibits the Profibrotic Effects of Transforming Growth Factor-β1 in Hepatic Stellate Cells by Reducing Autophagy. Digestive diseases and sciences 16 29196956
2013 Helicobacter pylori infection and expressions of apoptosis-related proteins p53, ASPP2 and iASPP in gastric cancer and precancerous lesions. Pathologie-biologie 16 23528480
2013 Attenuated expression of apoptosis stimulating protein of p53-2 (ASPP2) in human acute leukemia is associated with therapy failure. PloS one 16 24312201
2022 Dysregulated hepatic lipid metabolism and gut microbiota associated with early-stage NAFLD in ASPP2-deficiency mice. Frontiers in immunology 15 36466835
2022 TP53BP2: Roles in suppressing tumorigenesis and therapeutic opportunities. Genes & diseases 15 37492707
2018 HDAC1-induced epigenetic silencing of ASPP2 promotes cell motility, tumour growth and drug resistance in renal cell carcinoma. Cancer letters 15 29890207
2013 Regulation of ASPP2 interaction with p53 core domain by an intramolecular autoinhibitory mechanism. PloS one 15 23472201
2020 ASPP2 suppression promotes malignancy via LSR and YAP in human endometrial cancer. Histochemistry and cell biology 14 32266459
2017 ASPP2 Plays a Dual Role in gp120-Induced Autophagy and Apoptosis of Neuroblastoma Cells. Frontiers in neuroscience 14 28392757
2017 Dioscin enhances osteoblastic cell differentiation and proliferation by inhibiting cell autophagy via the ASPP2/NF-κβ pathway. Molecular medicine reports 14 28849197
2007 Insights into the structure and protein-protein interactions of the pro-apoptotic protein ASPP2. Biochemical Society transactions 14 17956256
2019 Alternative splicing of the tumor suppressor ASPP2 results in a stress-inducible, oncogenic isoform prevalent in acute leukemia. EBioMedicine 13 30952616
2018 ASPP2 enhances chemotherapeutic sensitivity through the down-regulation of XIAP expression in a p53 independent manner in hepatocellular carcinoma. Biochemical and biophysical research communications 13 30528232
2019 Effect of miR-21 on apoptosis in hepatoblastoma cell through activating ASPP2/p38 signaling pathway in vitro and in vivo. Artificial cells, nanomedicine, and biotechnology 12 31535570
2016 ASPP2 suppresses stem cell-like characteristics and chemoresistance by inhibiting the Src/FAK/Snail axis in hepatocellular carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 12 27473084
2016 ΔN-ASPP2, a novel isoform of the ASPP2 tumor suppressor, promotes cellular survival. Biochemical and biophysical research communications 12 27939881
2013 Phosphorylation of ASPP2 by RAS/MAPK pathway is critical for its full pro-apoptotic function. PloS one 12 24312625
2022 ASPP2 Coordinates ERS-Mediated Autophagy and Apoptosis Through mTORC1 Pathway in Hepatocyte Injury Induced by TNF-α. Frontiers in pharmacology 11 35418864
2019 miR-219a-5p Ameliorates Hepatic Ischemia/Reperfusion Injury via Impairing TP53BP2. Digestive diseases and sciences 11 30796685
2019 RASSF10 Is a TGFβ-Target That Regulates ASPP2 and E-Cadherin Expression and Acts as Tumor Suppressor That Is Epigenetically Downregulated in Advanced Cancer. Cancers 11 31817988
2013 Aspp2 negatively regulates body growth but not developmental timing by modulating IRS signaling in zebrafish embryos. General and comparative endocrinology 11 24362258
2008 p53 target DDA3 binds ASPP2 and inhibits its stimulation on p53-mediated BAX activation. Biochemical and biophysical research communications 11 18793611
2016 Exogenous p53 and ASPP2 expression enhances rAdV-TK/ GCV-induced death in hepatocellular carcinoma cells lacking functional p53. Oncotarget 10 26934443
2021 ASPP2 inhibits hepatitis B virus replication by preventing nucleus translocation of HSF1 and attenuating the transactivation of ATG7. Journal of cellular and molecular medicine 9 34085409
2020 Truncated ASPP2 Drives Initiation and Progression of Invasive Lobular Carcinoma via Distinct Mechanisms. Cancer research 9 32060147
2017 TP53-based interaction analysis identifies cis-eQTL variants for TP53BP2, FBXO28, and FAM53A that associate with survival and treatment outcome in breast cancer. Oncotarget 9 28179588
2017 Synergistic inhibitory effects on hepatocellular carcinoma with recombinant human adenovirus Aspp2 and oxaliplatin via p53-independent pathway in vitro and in vivo. International journal of oncology 9 28902369
2016 Small Interfering RNA Targeted to ASPP2 Promotes Progression of Experimental Proliferative Vitreoretinopathy. Mediators of inflammation 9 27378826
2016 ASPP2 involvement in p53-mediated HIV-1 envelope glycoprotein gp120 neurotoxicity in mice cerebrocortical neurons. Scientific reports 8 27625111
2015 The tumor suppressor proteins ASPP1 and ASPP2 interact with C-Nap1 and regulate centrosome linker reassembly. Biochemical and biophysical research communications 8 25660448
2005 Mdm2 and mdmX prevent ASPP1 and ASPP2 from stimulating p53 without targeting p53 for degradation. Oncogene 8 15782125
2019 TP53BP2 decreases cell proliferation and induces autophagy in neuroblastoma cell lines. Oncology letters 7 31186708
2022 ASPP2 promotes cell apoptosis in cervical cancer through inhibiting autophagy. Experimental and therapeutic medicine 6 36340606
2017 Identification of TP53BP2 as a Novel Candidate Gene for Primary Open Angle Glaucoma by Whole Exome Sequencing in a Large Multiplex Family. Molecular neurobiology 6 28150229
2016 ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome. Cell death and differentiation 6 27447114
2015 An Intrinsically Disordered Region in the Proapoptotic ASPP2 Protein Binds to the Helicobacter pylori Oncoprotein CagA. Biochemistry 6 25963096
2014 The E3 ubiquitin ligase Itch and Yap1 have antagonistic roles in the regulation of ASPP2 protein stability. FEBS letters 6 25436413
2013 Nucleostemin and ASPP2 expression is correlated with pituitary adenoma proliferation. Oncology letters 6 24179515
2010 Cell type specific expression of the apoptosis stimulating protein (ASPP-2) in human tissues. Acta microbiologica et immunologica Hungarica 6 21183427
2021 Knockout of ASPP2 promotes DEN-induced hepatocarcinogenesis via the NF-κB pathway in mice. Cancer gene therapy 5 33558702

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