Affinage

TP53BP2

Apoptosis-stimulating of p53 protein 2 · UniProt Q13625

Length
1128 aa
Mass
125.6 kDa
Annotated
2026-04-28
100 papers in source corpus 48 papers cited in narrative 47 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASPP2/TP53BP2 is a multidomain scaffold protein that integrates p53-family-dependent apoptosis, epithelial cell polarity, Hippo pathway signaling, and Ras-MAPK output. Its C-terminal ankyrin repeats and SH3 domain bind the DNA-binding domains of p53, p63, and p73, selectively stimulating transcription of pro-apoptotic targets (Bax, PUMA, PIG3) over cell-cycle arrest genes; this interaction is regulated by MAPK phosphorylation (which enhances p53 binding), intramolecular autoinhibition by its disordered proline-rich domain, and competitive displacement by Bcl-2, NF-κB p65, and pathogen effectors such as H. pylori CagA (PMID:8875926, PMID:14729977, PMID:24312625, PMID:18448430, PMID:21562218). Through its N-terminal Ras-association domain ASPP2 binds Ras-GTP to promote Raf dimerization and ERK signaling, contributing to oncogene-induced senescence, and through its PAR-3 interaction it maintains apical–basal polarity and tight-junction integrity, a function modulated by FIH-1-catalyzed asparagine hydroxylation and regulated by Siah2/Itch-mediated proteasomal degradation (PMID:23248303, PMID:20619648, PMID:23606740, PMID:23644657). ASPP2 also acts as a PP1 scaffold to dephosphorylate TAZ and YAP at cell junctions, linking it to Hippo pathway control, and stimulates CSK to inactivate Src, suppressing invasion (PMID:21189257, PMID:25360797, PMID:27473084).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1994 High

    Systematic mutagenesis of the p53 core domain established that specific residues (notably R175) are required for 53BP2 binding but dispensable for DNA binding, separating p53's protein-interaction and transcriptional surfaces.

    Evidence Alanine-scanning mutagenesis in yeast two-hybrid

    PMID:7969167

    Open questions at the time
    • Binding affinity not quantified
    • Structural basis of selectivity unknown at this stage
  2. 1996 High

    Crystal structure of p53 core domain–53BP2 revealed an unconventional SH3-mediated contact at the L3 loop plus ankyrin repeat binding at L2, explaining why the six most common p53 cancer hotspot mutations disrupt ASPP2 binding and establishing the structural basis of this tumor-suppressive interaction.

    Evidence X-ray crystallography and in vitro mutagenesis binding assays

    PMID:8668206 PMID:8875926

    Open questions at the time
    • Full-length ASPP2 structure unknown
    • In vivo relevance of 53BP2–p53 contact not yet demonstrated
  3. 2000 High

    Demonstrating that ASPP2 protein levels rise after UV irradiation independently of p53, and that ASPP2 gain/loss-of-function alters apoptotic threshold, established ASPP2 as a DNA-damage-inducible pro-apoptotic effector rather than a passive p53 partner.

    Evidence Inducible expression, antisense knockdown, clonogenic survival assay

    PMID:11027272

    Open questions at the time
    • Kinase/signaling pathway mediating UV-induced stabilization not identified
    • In vivo role in DNA damage response not tested
  4. 2004 High

    Identification of ASPP2 binding to p63 and p73 and RNAi epistasis showing ASPP2's apoptotic output requires p63/p73 broadened ASPP2 from a p53-specific cofactor to a common activator of all three p53 family members for pro-apoptotic gene selectivity.

    Evidence Co-IP, reporter assays, siRNA of p63/p73 in p53-null cells

    PMID:14729977

    Open questions at the time
    • Structural basis for selectivity toward apoptotic vs. cell-cycle arrest promoters unknown
    • Whether all three family members are relevant in the same tissue context unclear
  5. 2005 High

    Discovery that ASPP2 is an E2F transcriptional target peaking in early S-phase, and is regulated by proteasomal degradation (stabilized by bortezomib), revealed the dual transcriptional and post-translational control circuits governing ASPP2 abundance.

    Evidence ChIP of E2F on ASPP2 promoter; cycloheximide chase, ubiquitination assay, bortezomib treatment

    PMID:15592436 PMID:16091363

    Open questions at the time
    • Identity of the E3 ubiquitin ligase(s) responsible not yet known at this stage
    • Whether cell-cycle-dependent ASPP2 oscillation has functional consequence for apoptosis unclear
  6. 2008 High

    Biophysical mapping showed ASPP2's proline-rich domain is natively disordered and forms an intramolecular autoinhibitory contact with its own Ank-SH3 domains, revealing how ASPP2 partner interactions are gated; concurrently, quantitative binding studies defined the Bcl-2 BH4-domain interaction and the 1:1 stoichiometry with p53/p63/p73.

    Evidence CD, NMR, SPR, ITC, peptide array, fluorescence anisotropy

    PMID:18448430 PMID:18676979 PMID:18719108

    Open questions at the time
    • Signal or modification that relieves autoinhibition in cells not identified
    • Relative affinities for p53 vs. Bcl-2 vs. NF-κB in a cellular context unknown
  7. 2010 High

    Demonstration that ASPP2 binds PAR-3 and is required for tight-junction formation, apical polarity, and PAR-complex activity—both in polarized epithelia and neural progenitors in vivo—uncovered a major p53-independent function in epithelial tissue organization.

    Evidence ASPP2-deficient mouse CNS, siRNA in polarized MDCK cells, co-IP, immunofluorescence

    PMID:20619648 PMID:20619750

    Open questions at the time
    • Whether polarity and apoptotic functions are co-regulated or independent unclear
    • Structural basis of ASPP2-PAR-3 interaction not resolved
  8. 2012 High

    Discovery that the ASPP2 N-terminal Ras-association domain binds Ras-GTP, promotes B-Raf/C-Raf dimerization and ERK activation, and is required for oncogene-induced senescence placed ASPP2 as an effector linking Ras signaling to both MAPK output and p53 apoptotic function.

    Evidence Ras-GTP pulldown, pERK blot, Raf dimerization assay, senescence assay, isoform comparison

    PMID:23248303 PMID:23392125

    Open questions at the time
    • Structural basis of Ras-ASPP2 interaction not determined
    • Whether Ras-ASPP2 binding is cooperative with p53 binding in cells unclear
  9. 2013 High

    Multiple regulatory layers were delineated in a single year: MAPK phosphorylation enhances ASPP2-p53 binding and apoptosis; FIH-1 hydroxylation at N986 selectively promotes PAR-3 (not p53) binding; Siah2 ubiquitinates ASPP2 under hypoxia to disrupt polarity; and ASPP2 stimulates CSK to inactivate Src—collectively revealing how distinct post-translational modifications route ASPP2 toward apoptotic vs. polarity vs. invasion-suppressive outputs.

    Evidence In vitro kinase assay with phospho-mutants, MS-identified hydroxylation, Siah2 ubiquitination assay in 3D culture, CSK kinase assay

    PMID:23606740 PMID:23644657 PMID:23671128 PMID:24312625

    Open questions at the time
    • How these modifications are coordinated in a single cell is unknown
    • Whether phosphorylation relieves autoinhibition is untested
  10. 2014 High

    ASPP2 was shown to scaffold PP1 to dephosphorylate TAZ and YAP at cell junctions, and separately to form an ASPP2-β-catenin-E-cadherin complex that blocks ZEB1 transcription, establishing ASPP2 as a dual Hippo-pathway and EMT regulator at the junction-cytoplasm interface.

    Evidence PP1 scaffold dephosphorylation assay, co-IP of ternary complex, in vivo mouse colonic epithelium and metastasis model

    PMID:21189257 PMID:25344754 PMID:25360797

    Open questions at the time
    • Structural basis of PP1 scaffolding unknown
    • Whether YAP/TAZ dephosphorylation and β-catenin stabilization are coupled unclear
  11. 2014 High

    Crystal structure of H. pylori CagA bound to the ASPP2 proline-rich region revealed how a pathogen effector hijacks ASPP2 to degrade p53 and disrupt PAR-complex polarity, providing a structural explanation for infection-driven oncogenesis.

    Evidence X-ray crystallography, structure-guided mutagenesis, gastric organoid infection model

    PMID:21562218 PMID:24474782 PMID:31964836

    Open questions at the time
    • Whether CagA binding relieves autoinhibition is untested
    • Therapeutic blockade with ASPP2 peptides not validated in patients
  12. 2020 High

    A truncated ASPP2 isoform (t-ASPP2) was found to drive PP1-dependent actomyosin relaxation enabling E-cadherin-deficient cell survival, while also activating YAP—mechanistically separating two PP1-dependent outputs (actomyosin relaxation for tumor initiation vs. YAP for progression) in invasive lobular carcinoma.

    Evidence Mouse genetic mammary ILC model, PP1 interaction mapping, domain mutants

    PMID:32060147

    Open questions at the time
    • How t-ASPP2 is generated in human tumors unclear
    • Whether full-length and truncated ASPP2 compete for PP1 pools unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions remain: no full-length ASPP2 structure exists to explain how autoinhibition, phosphorylation, and hydroxylation are spatially integrated; the signals that switch ASPP2 between its apoptotic, polarity, Hippo, and Ras-effector functions in the same cell are undefined; and the physiological relevance of ASPP2-SREBP2 and ASPP2-HSF1 interactions in normal tissues has not been established.
  • No full-length structure or cryo-EM model
  • No systematic tissue-specific interactome
  • Relative contribution of ASPP2 vs. ASPP1 vs. iASPP in vivo poorly resolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0140110 transcription regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-5357801 Programmed Cell Death 5 R-HSA-1500931 Cell-Cell communication 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-9612973 Autophagy 3 R-HSA-168256 Immune System 2
Partners
BCL2CSKPARD3PPP1CATP53TP63TP73YAP1
Complex memberships
ASPP2-PP1 phosphatase scaffoldASPP2-β-catenin-E-cadherin complexPAR polarity complex (ASPP2-PAR-3)

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Crystal structure of p53 core domain bound to 53BP2 (ASPP2 C-terminus) revealed that the SH3 domain binds the L3 loop of p53 in a manner distinct from canonical SH3-polyproline interactions, and an ankyrin repeat binds the L2 loop of p53; the binding site overlaps the DNA-binding surface of p53, and the six most frequently mutated p53 cancer hotspots disrupt 53BP2 binding in vitro. X-ray crystallography and in vitro binding assays Science High 8875926
1996 53BP2/ASPP2 interacts with both Bcl-2 and p53 via its ankyrin repeats and SH3 domain; Bcl-2 and p53 compete for binding to 53BP2; overexpression of 53BP2 increases cells at G2/M and 53BP2 partially colocalizes with Bcl-2 in the cytoplasm. Yeast two-hybrid, in vitro GST pulldown with bacterially expressed proteins, competition binding assays, immunofluorescence Molecular and cellular biology High 8668206
1994 The p53 DNA-binding domain contains distinct residues for interaction with 53BP2 versus DNA versus SV40 Large T antigen; alanine substitution at R175 nearly eliminated 53BP2 (and 53BP1) binding without affecting DNA binding or transactivation, implicating R175 as critical for 53BP2 interaction. Alanine-scanning mutagenesis in yeast two-hybrid system with transcriptional readout Molecular and cellular biology High 7969167
1998 Both 53BP1 and 53BP2 enhance p53-mediated transcriptional activation in cells; 53BP2 localizes exclusively to the cytoplasm regardless of p53 co-expression, and p53 cannot bind simultaneously to 53BP2 and to consensus DNA. Immunofluorescence, reporter gene transactivation assay, competitive binding The Journal of biological chemistry Medium 9748285
1999 NF-κB p65 subunit binds to 53BP2/ASPP2 via its ankyrin repeats and SH3 domain; co-expression of p65 inhibits 53BP2-induced apoptosis; full-length GFP-53BP2 shows punctate perinuclear cytoplasmic distribution whereas N-terminal half is cytoplasmic and C-terminal half is nuclear. Yeast two-hybrid, in vitro pulldown, mammalian two-hybrid, GFP localization, apoptosis assay Oncogene Medium 10498867
2000 53BP2/ASPP2 protein levels increase after UV irradiation in a p53-independent manner; wild-type p53 suppresses basal 53BP2 protein levels; conditional expression of 53BP2 lowers the apoptotic threshold after UV damage, and antisense attenuation of 53BP2 induction enhances clonogenic survival, demonstrating 53BP2 is a DNA damage-inducible pro-apoptotic protein. Inducible expression system, antisense oligonucleotides, clonogenic survival assay, western blot Molecular and cellular biology High 11027272
2004 ASPP1 and ASPP2 bind p63 and p73 directly in vitro and in vivo, and stimulate transactivation of apoptotic target genes (Bax, PIG3, PUMA) but not cell-cycle arrest genes (mdm2, p21); RNAi of p63/p73 abolishes the p53-independent apoptotic function of ASPP1/2, identifying them as common activators of all p53 family members. Co-immunoprecipitation, luciferase reporter assay, RNA interference, endogenous gene expression analysis Molecular and cellular biology High 14729977
2004 Hepatitis C virus core protein interacts with ASPP2 and competes with p53 for ASPP2 binding in vitro; core protein expression inhibits p53-mediated apoptosis enhanced by ASPP2 without affecting p53 transcriptional activity on Bax or p21 promoters. Yeast two-hybrid, in vitro competition binding, apoptosis assay, reporter gene assay Biochemical and biophysical research communications Medium 14985081
2004 TP53BP2 encodes two protein isoforms, 53BP2S (short, 1005 aa) and 53BP2L/ASPP2 (long, 1128 aa), generated by alternative splicing involving exon 3. RT-PCR, genomic sequencing, expression analysis across cell lines and tissues Biochemical and biophysical research communications Medium 14766226
2005 ASPP2/53BP2L is an E2F transcriptional target; E2F-1, -2, and -3 bind the ASPP2 promoter in vivo and activate ASPP2 expression; ASPP2 levels peak in early S-phase consistent with E2F target gene kinetics. Chromatin immunoprecipitation, promoter-luciferase reporter assay, promoter mutational analysis, endogenous mRNA/protein induction Cell death and differentiation High 15592436 15731768
2005 ASPP2 protein is degraded by the proteasome; proteasomal inhibition (including clinically used bortezomib) and anthracyclines increase ASPP2 protein but not mRNA levels, increase ASPP2 half-life, and the central region of ASPP2 is ubiquitinated; siRNA knockdown of ASPP2 attenuates bortezomib-induced apoptosis preferentially in wild-type p53 cells. Proteasome inhibitor treatment, cycloheximide chase (half-life), ubiquitination assay, siRNA knockdown, apoptosis assay The Journal of biological chemistry High 16091363
2005 53BP2 localizes to mitochondria and induces apoptosis through the mitochondrial death pathway, as evidenced by depression of mitochondrial transmembrane potential and caspase-9 activation; PARP cleavage and annexin V staining confirm apoptosis. Subcellular fractionation, mitochondrial membrane potential assay, caspase-9 activation, annexin V staining, PARP cleavage Genes to cells Medium 15743414
2005 Mdm2 and MdmX prevent ASPP1 and ASPP2 from stimulating p53 apoptotic function by binding and inhibiting p53 transcriptional activity, without targeting p53 for degradation; both the DNA-binding and transactivation functions of p53 are required for ASPP proteins to stimulate p53 apoptotic function. p53/mdm2 mutant analysis, reporter gene transactivation assay Oncogene Medium 15782125
2006 Binding of 53BP2 (ASPP2 C-terminus) to p53 core domain is mutually exclusive with DNA binding for both pro-apoptotic (Bax, PIG3) and non-apoptotic (GADD45, p21) response elements, with no evidence for a ternary 53BP2-p53-DNA complex; various oncogenic p53 mutations differentially affect DNA and 53BP2 binding. Isothermal titration calorimetry, fluorescence anisotropy, NMR, surface plasmon resonance The Journal of biological chemistry High 16887812
2008 ASPP2 C-terminal ankyrin repeats and SH3 domain (Ank-SH3) interact with Bcl-2 via two sites: the conserved BH4 motif and a binding site for proapoptotic regulators; Bcl-2 binding is tighter than for Bcl-XL or Bcl-W due to two positively charged non-conserved residues; ASPP2 binds three loops of the Ank-SH3 domain simultaneously; ASPP2 is proposed to induce apoptosis by inhibiting functional sites of antiapoptotic Bcl-2 proteins. Peptide array screening, surface plasmon resonance, isothermal titration calorimetry, computational docking/molecular dynamics Proceedings of the National Academy of Sciences of the United States of America High 18719108
2008 ASPP1 and ASPP2 C-termini bind directly to DNA-binding domains of p53, p63, and p73 with 1:1 stoichiometry and Kd in the low micromolar range; ASPP2 (but not ASPP1) forms a binary complex with PUMA that displaces p53 and p73. ITC, fluorescence anisotropy, EMSA, size-exclusion chromatography Nucleic acids research High 18676979
2008 The proline-rich domain (Pro) of ASPP2 is natively unfolded and forms an intramolecular autoinhibitory interaction with the Ank-SH3 domains; this intramolecular interaction inhibits the ability of Ank-SH3 to bind partner-derived peptides (e.g., NF-κB), suggesting a regulatory mechanism for ASPP2 intermolecular interactions. CD spectroscopy, NMR, peptide array screening, SPR, size-exclusion chromatography The Journal of biological chemistry High 18448430
2009 ASPP2 interacts with Par-3 and controls apical/junctional localization of Par-3 in neural progenitors in vivo; ASPP2 loss disrupts tight/adherens junctions, impairs interkinetic nuclear migration, and leads to formation of neuroblastic rosettes resembling primitive neuroepithelial tumors; junctional localization of ASPP2 and Par-3 is interdependent. In vivo mouse CNS development model (ASPP2-deficient), immunofluorescence, co-immunoprecipitation 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 defects in tight junction formation, apical membrane maintenance, and PAR-3 localization; ASPP2-PAR-3 interaction is required for formation of an active PAR complex. Co-immunoprecipitation, siRNA knockdown, immunofluorescence in polarized epithelial cells Current biology High 20619648
2010 PP1A dephosphorylates TAZ at Ser-89 and Ser-311, promoting TAZ nuclear translocation and stability; ASPP2 facilitates the interaction between TAZ and PP1 to promote TAZ dephosphorylation, thereby antagonizing LATS kinase-mediated TAZ inhibition. In vitro phosphatase assay, co-immunoprecipitation, subcellular fractionation, siRNA knockdown The Journal of biological chemistry High 21189257
2011 H. pylori CagA associates with ASPP2 upon delivery into host cells; the CagA-ASPP2 interaction recruits p53 to ASPP2 and leads to enhanced p53 degradation, reducing apoptosis; ASPP2 is required for CagA-dependent resistance to doxorubicin-induced apoptosis. Co-immunoprecipitation in infected cells, p53 degradation assay, apoptosis assay in infected vs. uninfected cells Proceedings of the National Academy of Sciences of the United States of America High 21562218
2012 ASPP2 N-terminus contains a Ras-association domain that binds Ras-GTP at the plasma membrane; ASPP2 stimulates Ras-induced signaling by promoting Ras-GTP loading, B-Raf/C-Raf dimerization, and C-Raf phosphorylation, thereby increasing pERK1/2; ASPP2 loss attenuates H-RasV12-induced senescence in normal human cells; the short isoform BBP/53BP2S lacking the N-terminus is defective in Ras-GTP binding and Raf/MEK/ERK stimulation. Co-immunoprecipitation with Ras-GTP pulldown, pERK western blot, B-Raf/C-Raf dimerization assay, C-Raf phosphorylation, siRNA knockdown, senescence assay Proceedings of the National Academy of Sciences of the United States of America High 23248303
2012 Crystal structure of p73 DNA-binding domain in complex with ASPP2 ankyrin repeat and SH3 domains reveals that ASPP2 binding is preserved despite p73 having a divergent L2 loop (with a two-residue insertion); binding is accommodated by conformational changes in both the ankyrin repeat and SH3 domains of ASPP2. X-ray crystallography Journal of molecular biology High 22917970
2013 ASPP2 MAPK phosphorylation (by RAS/MAPK pathway) is required for full pro-apoptotic function; phosphorylated ASPP2 shows increased binding to p53 and enhanced transactivation of pro-apoptotic genes; a non-phosphorylatable ASPP2 mutant fails to enhance apoptosis. In vitro kinase assay, phosphorylation mutant analysis, co-immunoprecipitation, reporter gene assay, apoptosis assay PloS one High 24312625
2013 ASPP1 and ASPP2 preferentially bind active Ras (Ras-GTP) via N-terminal RAS-association domains; ASPP2 colocalizes with and contributes to RAS membrane localization; ASPP1/2 cooperate with oncogenic RAS to enhance p53 transcription and apoptotic function in cancer cells. Co-immunoprecipitation with Ras-GTP, immunofluorescence co-localization, reporter gene assay, apoptosis assay Cell death and differentiation Medium 23392125
2013 The proline-rich domain of ASPP2 competes with p53 core domain for binding to the n-src loop of the ASPP2 SH3 domain, providing experimental evidence for intramolecular autoinhibition of p53 binding; p53 core domain displaces NF-κB (residues 303-332) from the RT loop of ASPP2 SH3, indicating overlapping but partly distinct binding sites for p53 and NF-κB; Bcl-2-derived peptides bind distinct sites in ASPP2 Ank-SH3 from p53. Fluorescence anisotropy competition assays PloS one Medium 23472201
2013 ASPP2 inhibits ΔNp63 expression through binding IκB and enhancing nuclear RelA/p65 (NF-κB), which mediates transcriptional repression of p63; haploinsufficiency of p63 but not p53 prevents ASPP2-deficient BALB/c mice from developing squamous cell carcinoma, placing ASPP2 upstream of p63 via NF-κB. Mouse genetic epistasis (double heterozygous), co-immunoprecipitation, reporter gene assay Proceedings of the National Academy of Sciences of the United States of America High 24127607
2013 FIH-1 (factor inhibiting HIF-1) hydroxylates ASPP2 at asparagine 986 within the ankyrin repeat domain; FIH-1 depletion impairs Par-3 binding to ASPP2 and causes ASPP2 to relocate from cell-cell contacts to the cytosol, without affecting ASPP2-p53 interaction or apoptosis. Mass spectrometry identification of hydroxylation site, FIH-1 knockdown, co-immunoprecipitation, immunofluorescence Journal of cell science High 23606740
2013 Siah2 ubiquitin ligase binds ASPP2 (identified by LC-MS/MS), ubiquitinates and promotes proteasomal degradation of ASPP2 via degron motifs; under hypoxia, Siah2 upregulation decreases ASPP2 levels, impairs tight junction integrity and apical polarity in 3D culture; Siah2 inhibition increases ASPP2 and maintains polarity. LC-MS/MS interactome, co-immunoprecipitation, ubiquitination assay, siRNA knockdown, 3D organotypic culture Oncogene High 23644657
2013 ASPP2 interacts with APP-BP1 (NEDD8 activating enzyme subunit); ASPP2 inhibits APP-BP1-mediated NEDD8 conjugation to Cullin-1 and blocks APP-BP1-induced cell proliferation and neuronal apoptosis; the interaction maps to ASPP2(332-483) N-terminal domain. Co-immunoprecipitation in non-transfected cells, neddylation assay, neuronal apoptosis assay Journal of neurochemistry Medium 12694406
2014 ASPP2 induces MET (mesenchymal-to-epithelial transition) through its PAR3-binding N-terminus independently of p53 binding; ASPP2 forms an ASPP2-β-catenin-E-cadherin ternary complex preventing β-catenin from transactivating ZEB1; ASPP2 also inhibits β-catenin N-terminal phosphorylation to stabilize the β-catenin-E-cadherin complex; ASPP2 limits RAS-driven invasion and inhibits metastasis in vivo. Co-immunoprecipitation (ternary complex), in vivo mouse metastasis model, β-catenin phosphorylation assay, domain-deletion mutants Nature cell biology High 25344754
2014 Crystal structure (2.0 Å) of CagA N-terminal subdomain bound to a 7-kDa proline-rich peptide of ASPP2 reveals CagA forms a three-helix bundle with loop insertions creating a deep binding cleft for a conserved 20-aa ASPP2 peptide; ASPP2 forms an extended helix burying >1000 Ų of surface; structure-based point mutations in either CagA or ASPP2 disrupt binding in vitro and in vivo and alter ASPP2 function. X-ray crystallography, yeast two-hybrid, biochemical interaction assays, structure-guided mutagenesis Proceedings of the National Academy of Sciences of the United States of America High 24474782
2014 ASPP2 forms an apical-lateral polarity complex with PP1 and junctional YAP at tight junctions in polarized epithelial cells; ASPP2 acts as a scaffold bridging PP1 and YAP, directly inducing dephosphorylation and activation of junctional YAP; this mechanism operates in the murine colonic epithelium in vivo. Co-immunoprecipitation, siRNA knockdown, phosphorylation assay, in vivo mouse colonic epithelium analysis PloS one High 25360797
2014 Itch E3 ubiquitin ligase binds ASPP2 via Itch WW domains interacting with ASPP2 PPXY motifs, mediating ASPP2 ubiquitination and degradation; Yap1 competes with Itch for ASPP2 binding and prevents Itch-mediated ASPP2 degradation, establishing antagonistic regulation of ASPP2 protein stability. Co-immunoprecipitation, ubiquitination assay, competition binding, overexpression and knockdown FEBS letters Medium 25436413
2014 ASPP2 promotes autophagic apoptosis in hepatoma cells through CHOP expression in a p53/p73-independent manner; CHOP reduces Bcl-2, releasing Beclin-1 to initiate autophagy; nuclear ASPP2-Bcl-2 complex (CHOP-dependent) prevents remaining Bcl-2 from returning to cytoplasm, cooperating with DRAM to induce autophagic apoptosis. Overexpression, siRNA knockdown, co-immunoprecipitation (nuclear Bcl-2-ASPP2), autophagy flux assay, apoptosis assay Cell death & disease Medium 25032846
2015 ASPP2 promotes centrosome linker reassembly at the end of mitosis by interacting with centrosome linker protein C-Nap1; ASPP2 facilitates C-Nap1-PP1α interaction and antagonizes NEK2A-mediated C-Nap1 phosphorylation (Ser2417/2421) in a PP1-dependent manner; co-depletion of ASPP1/2 inhibits C-Nap1 dephosphorylation and reassociation with centrosomes. Co-immunoprecipitation, siRNA knockdown, phosphorylation assay, centrosome localization by immunofluorescence Biochemical and biophysical research communications Medium 25660448
2016 CagA-ASPP2 interaction promotes remodeling of the PAR polarity complex and causes loss of cell polarity in H. pylori-infected gastric organoids; inhibitors of EGFR signaling or a CagA-binding ASPP2 peptide prevent polarity loss and decrease H. pylori survival in infected organoids. Human gastric organoid infection model, high-content imaging inhibitor screen, ASPP2 peptide blockade Proceedings of the National Academy of Sciences of the United States of America High 31964836
2017 ASPP2 suppresses TGF-β1-induced EMT in gastric cancer by interacting with E3 ubiquitin ligase ITCH and inhibiting ITCH-mediated degradation of Smad7, a negative regulator of TGF-β1-Smad2/3 signaling. Co-immunoprecipitation, Smad7 degradation assay, EMT markers, invasion assay Cancer letters Medium 28400336
2019 ASPP2 interacts with SREBP-2 in the nucleus and restricts SREBP-2 transcriptional activity on mevalonate pathway genes (including HMGCR); ASPP2 depletion increases cholesterol levels and enhanced tumor-initiating capability, reversible by simvastatin. Co-immunoprecipitation, gene expression profiling, cholesterol assay, simvastatin rescue in vitro and in vivo Cell death & disease Medium 31685796
2013 ASPP2 inhibits autophagy in hepatocellular carcinoma by: (1) forming an ASPP2-p65/RelA-IκBα complex that prevents IκBα phosphorylation and p65 nuclear translocation to reduce BECN1 transcription; and (2) binding BECN1 directly, decreasing PIK3C3 and UVRAG association while increasing Rubicon binding in the PIK3C3 complex. Co-immunoprecipitation, reporter gene assay, autophagic flux assay, siRNA knockdown, in vivo xenograft Cell death & disease Medium 27929538
2009 The DEAD box protein Ddx42p physically interacts with ASPP2 via the Ddx42p C-terminus and the mid-N-terminal/ankyrin-SH3 regions of ASPP2; Ddx42p overexpression inhibits ASPP2-induced apoptosis and shifts ASPP2 subcellular distribution from cytoplasm+nucleus to predominantly cytoplasm. Co-immunoprecipitation, overexpression/knockdown, apoptosis assay, immunofluorescence Oncogene Medium 19377511
2014 STAT1 directly activates ASPP2 transcription in response to LPS/IFN via an NF-κB RELA/p65-independent but STAT1-dependent pathway; LPS induces nuclear ASPP2 at the blood-CSF barrier in vivo and ASPP2 mediates LPS-induced apoptosis; ASPP2-deficient brains show enhanced neuroinflammation. LPS/IFN treatment in multiple cell types, STAT1 dependence via siRNA, in vivo LPS maternal inflammation mouse model, ASPP2-deficient brain analysis Proceedings of the National Academy of Sciences of the United States of America Medium 24958857
2021 ASPP2 binds HSF1 in the cytoplasm of HBV-infected cells, preventing HSF1 nuclear translocation and thereby inhibiting HSF1-mediated transactivation of ATG7; reduced ATG7 expression decreases HBV-induced hepatocyte autophagy and inhibits HBV replication. Co-immunoprecipitation, subcellular fractionation, ATG7 promoter analysis, adenovirus-mediated overexpression, HBV replication assay Journal of cellular and molecular medicine Medium 34085409
2020 Truncated ASPP2 (t-ASPP2, N-terminal truncation) induces actomyosin relaxation via PP1 interaction enabling E-cadherin-deficient mammary epithelial cell survival on stiff matrices; t-ASPP2 also activates YAP; actomyosin relaxation (PP1-dependent) drives ILC initiation while YAP activation drives tumor progression. Mouse genetic mammary ILC model, PP1 interaction mapping, actomyosin assay, domain mutants, YAP reporter Cancer research High 32060147
2013 ASPP2 physically interacts with C-terminal Src kinase (CSK) and stimulates CSK kinase activity, leading to Src inactivation and AP1-mediated downregulation of Snail expression, thereby suppressing HCC stemness and drug resistance. Co-immunoprecipitation, CSK kinase assay, pharmacologic Src inhibition, gene expression profiling Tumour biology Medium 27473084
2013 ASPP2 inactivation of Src is Csk-dependent and specific to ASPP2 (not ASPP1); ASPP2 expression in choriocarcinoma cells decreases Src-pY416 phosphorylation and reduces cell migration. Western blot for Src phosphorylation, RNAi of Csk, wound-healing migration assay, ASPP2 transfection Carcinogenesis Medium 23671128
2023 TP53BP2 downregulates SOCS2 expression, thereby facilitating JAK/STAT signaling and enhancing the IFN-α response in hepatocytes; loss of TP53BP2 decreased interferon-stimulated gene levels and reduced the anti-HBV effect of IFN-α. In vitro and in vivo experiments with TP53BP2 loss-of-function, SOCS2 expression analysis, JAK/STAT pathway readout Journal of hepatology Medium 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 185 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.) 94 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 87 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
2005 Apoptosis-stimulating protein of p53-2 (ASPP2/53BP2L) is an E2F target gene. Cell death and differentiation 50 15592436
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 49 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 49 24474782
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
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
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 40 24127607
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
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
2019 ASPP2 inhibits tumor growth by repressing the mevalonate pathway in hepatocellular carcinoma. Cell death & disease 26 31685796
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
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 Higher TP53BP2 expression is associated with HBsAg loss in peginterferon-α-treated patients with chronic hepatitis B. Journal of hepatology 22 37858684
2013 Downregulation of ASPP2 in choriocarcinoma contributes to increased migratory potential through Src signaling pathway activation. Carcinogenesis 22 23671128
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
2021 Sufentanil Protects the Liver from Ischemia/Reperfusion-Induced Inflammation and Apoptosis by Inhibiting ATF4-Induced TP53BP2 Expression. Inflammation 20 33751357
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 19 36752127
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
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
2022 Dysregulated hepatic lipid metabolism and gut microbiota associated with early-stage NAFLD in ASPP2-deficiency mice. Frontiers in immunology 14 36466835
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
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
2017 Dioscin enhances osteoblastic cell differentiation and proliferation by inhibiting cell autophagy via the ASPP2/NF-κβ pathway. Molecular medicine reports 13 28849197
2022 TP53BP2: Roles in suppressing tumorigenesis and therapeutic opportunities. Genes & diseases 12 37492707
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
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
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 8 34085409
2020 Truncated ASPP2 Drives Initiation and Progression of Invasive Lobular Carcinoma via Distinct Mechanisms. Cancer research 8 32060147
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
2014 [Phosphorylation status of ASPP2 modulates p53 apoptotic function in oxaliplatin-induced apoptosis of colorectal cancer HCT116 cells]. Zhonghua zhong liu za zhi [Chinese journal of oncology] 5 25241782