Affinage

Showing PPP1R13L — IASPP is a alias.

PPP1R13L

RelA-associated inhibitor · UniProt Q8WUF5

Length
828 aa
Mass
89.1 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PPP1R13L (iASPP) is an evolutionarily conserved oncoprotein and multifunctional scaffold whose canonical role is inhibition of p53-dependent apoptosis (PMID:12524540). It binds the p53 DNA-binding domain and proline-rich region, and the crystal structure of the p53-iASPP complex shows it displaces the p53 L1 loop to reshape DNA-binding site selectivity along a surface overlapping the HPV E6 footprint (PMID:16964264, PMID:31395738). iASPP function is governed by tightly regulated subcellular partitioning and post-translational control: cyclin B1/CDK1 phosphorylation disrupts iASPP dimerization, drives nuclear entry of the monomer, and exposes its p53-binding sites to enhance p53 inhibition (PMID:23623661), while caspase cleavage at SSLD294 generates an 80 kDa nuclear fragment that inhibits p53 and RelA/p65 more potently than the full-length protein (PMID:26646590). iASPP also acts as a noncanonical PP1-targeting subunit, engaging PP1 through an RNYF motif in its SH3 domain that is required for p53 inhibition (PMID:21998301). Its repressive activity extends beyond p53 to the p53-family transcription factors p63 and p73 and to NF-κB/RelA, integrating control of epithelial stratification, inflammation, and apoptosis (PMID:21930934, PMID:22538442, PMID:28069640). Independently of apoptosis, iASPP stabilizes stress-response and homeostatic effectors by competing with E3-ligase or adaptor partners: it competes with Nrf2 for Keap1 to suppress Nrf2 ubiquitination and reduce ROS (PMID:29033244), binds VHL to block HIF-1α degradation (PMID:35169254), competes with Gp78 to protect the Ca2+ channel TMCO1 (PMID:35121659), and competes with GRP78 for the ER-resident ligase RNF185 to modulate the unfolded-protein response (PMID:36380064). During cell division, iASPP couples to the cytoskeleton and mitotic machinery: it associates with EB1 via an SxIP motif and with Myosin-Ic to control cortical stiffness and spindle positioning (PMID:34705028), and targets PP1 to dephosphorylate CEP55 for cytokinetic abscission (PMID:29743530). At desmosomes, iASPP binds desmoplakin and desmin to maintain intercalated-disc integrity (PMID:25691752). Loss-of-function PPP1R13L mutation causes a human cardio-cutaneous syndrome with hypersensitive NF-κB-driven inflammation, and iASPP-deficient mice develop ARVC-like cardiac disease and cutaneous defects (PMID:25691752, PMID:28069640, PMID:29352264).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2003 High

    Established iASPP as a conserved inhibitor of p53 whose loss triggers p53-dependent apoptosis, defining it as an oncoprotein rather than a passive binding partner.

    Evidence RNAi in C. elegans and antisense RNA in human cells plus oncogenic transformation assays

    PMID:12524540

    Open questions at the time
    • Did not define the molecular contact surface on p53
    • Did not address p53-independent roles
  2. 2004 High

    Resolved that iASPP has cytoplasmic and nuclear isoforms, framing localization control as central to its activity.

    Evidence Subcellular fractionation, immunofluorescence and functional p53/apoptosis assays on long and short isoforms

    PMID:15489900

    Open questions at the time
    • Did not identify the signals or modifications driving nuclear translocation
    • Isoform-specific functional differences beyond localization unresolved
  3. 2006 High

    Defined the p53 proline-rich region as an additional iASPP contact and linked the codon-72 polymorphism to differential apoptotic output.

    Evidence Binding assays with p53 PRR and apoptosis assays in polymorphic variants

    PMID:16964264

    Open questions at the time
    • Atomic basis of selectivity not yet resolved
  4. 2007 High

    Showed that stress-induced p53 Ser46 phosphorylation and Pin1 actively dissociate the iASPP-p53 complex, establishing a regulated switch from inhibition to apoptosis.

    Evidence Co-IP, ChIP, reporter assays and Pin1-binding mutagenesis

    PMID:17906639

    Open questions at the time
    • Direct iASPP residues targeted by this switch not mapped
  5. 2009 Medium

    Linked iASPP overexpression to proteasomal p53 degradation and RAS/E1A-driven tumorigenesis, extending its action to p53 turnover.

    Evidence Overexpression in MEFs with MG132 and in vivo tumor formation

    PMID:19263435

    Open questions at the time
    • Mechanism by which iASPP promotes p53 degradation not defined
    • No direct ligase identified
  6. 2010 Medium

    Embedded iASPP in transcriptional feedback loops with both p53 and NF-κB, showing it is itself an inducible node responsive to DNA damage and viral signals.

    Evidence siRNA epistasis (p53/BAX/GADD45α), ChIP, EMSA and reporter assays; HBx induction via NF-κB

    PMID:20600029 PMID:20840860

    Open questions at the time
    • Quantitative dynamics of the feedback loops not modeled
    • Promoter occupancy in physiological settings limited
  7. 2011 High

    Identified iASPP as a noncanonical PP1-targeting subunit and broadened its transcriptional targets to p63 and NF-κB/RelA, revealing scaffold and phosphatase-recruitment functions beyond p53.

    Evidence RNYF/F815A mutagenesis with GST pulldown; knockout mouse with keratinocyte phenotypes and Co-IP for p63/RelA

    PMID:21930934 PMID:21998301

    Open questions at the time
    • PP1 substrates recruited by iASPP not yet enumerated
    • Structural basis of the noncanonical RNYF/PP1 interface unresolved
  8. 2011 Medium

    Connected iASPP to mitotic survival via separase activation, an early indication of p53-independent roles in cell division.

    Evidence Gain/loss-of-function in ovarian cancer cells with separase activity and mitotic catastrophe assays

    PMID:21926165

    Open questions at the time
    • Direct molecular link between iASPP and separase not established
    • Single cell-type context
  9. 2013 High

    Defined cyclin B1/CDK1 phosphorylation as the switch that disassembles iASPP dimers, drives nuclear entry, and exposes p53-binding sites, mechanistically coupling cell-cycle state to p53 inhibition.

    Evidence Phosphorylation, dimerization and nuclear fractionation assays with CDK1 inhibition; melanoma metastasis correlation

    PMID:23623661

    Open questions at the time
    • Phosphosite residues and their stoichiometry only partly defined
    • Phosphatase reversing this in vivo not identified here
  10. 2014 Medium

    Revealed apoptosis-independent roles in autophagy and neuronal survival, showing iASPP modulates Atg complex assembly and that its phospho-state tracks injury-induced p53 activity.

    Evidence siRNA with LC3 lipidation and Atg5-Atg12/Atg16L1 Co-IP; in vivo optic nerve axotomy with phospho-specific blotting

    PMID:24714389 PMID:24777476

    Open questions at the time
    • Direct iASPP-Atg interaction surface not mapped
    • Kinase/phosphatase controlling RGC iASPP phospho-state unknown
  11. 2015 High

    Established structural roles at desmosomes and additional regulators of apoptotic competence, broadening iASPP from a transcriptional inhibitor to a cytoarchitectural and acetyltransferase-stabilizing scaffold.

    Evidence Reciprocal Co-IP with desmoplakin/desmin and knockout mouse with ARVC-like phenotype; p300/CBP ubiquitination and caspase cleavage-site (SSLD294) mutagenesis with fractionation

    PMID:25675294 PMID:25691752 PMID:26646590

    Open questions at the time
    • How desmosomal and nuclear pools are partitioned unclear
    • Functional impact of the 80 kDa fragment in vivo not established
  12. 2017 High

    Identified the iASPP-Keap1-Nrf2 axis and a human loss-of-function disease, linking iASPP to oxidative-stress control, NF-κB-driven inflammation, and a defined cardio-cutaneous syndrome.

    Evidence DLT-motif competitive binding and ubiquitination assays for Keap1/Nrf2; human PPP1R13L stop-codon genetics with NF-κB EMSA/ChIP and mouse models

    PMID:28069640 PMID:29033244

    Open questions at the time
    • Tissue-specific balance between oncogenic and tumor-suppressive functions unresolved
    • How a single locus produces both cardiac and cutaneous phenotypes only partly explained
  13. 2018 High

    Defined iASPP as a PP1-CEP55 targeting factor required for cytokinetic abscission and identified additional protein partners, deepening its mitotic and homeostatic roles.

    Evidence Affinity purification/Co-IP with CEP55-Ser436 dephosphorylation and cytokinesis phenotypes; cell-type-specific knockout mice; NAF-1 peptide mapping

    PMID:29352264 PMID:29743530 PMID:30774867

    Open questions at the time
    • NAF-1 interaction lacks Co-IP/structural confirmation
    • Coordination of mitotic versus interphase iASPP pools unclear
  14. 2019 High

    Resolved the atomic mechanism of p53 inhibition: iASPP displaces the p53 L1 loop to alter DNA-binding site selectivity, distinguishing it from other p53-binding regulators.

    Evidence X-ray crystallography of the p53-iASPP complex with genome-wide binding-site analysis

    PMID:31395738

    Open questions at the time
    • Structures of iASPP with p63/p73 or RelA not determined
    • How phosphorylation alters the structural interface not visualized
  15. 2022 High

    Expanded the competitive-binding paradigm to VHL/HIF-1α, Gp78/TMCO1, and RNF185/GRP78, establishing iASPP as a general antagonist of E3-ligase substrate recognition controlling hypoxia, Ca2+, and ER-stress responses.

    Evidence Competitive Co-IP and ubiquitination assays with functional HIF-1α, Ca2+, and UPR readouts plus in vivo tumor models; EB1/Myo1c SxIP work on cortical mechanics

    PMID:34705028 PMID:35121659 PMID:35169254 PMID:36380064

    Open questions at the time
    • Whether one iASPP molecule integrates these axes or distinct pools act separately is unknown
    • Determinants of partner selectivity among competing E3 systems unresolved
  16. 2023 High

    Demonstrated a context-dependent tumor-suppressive role in KRAS- and inflammation-driven cancers acting through NF-κB/AP1 gene sets, sharpening the dual oncogene/tumor-suppressor model.

    Evidence Genetic KRASG12D;iASPP-deletion mouse models with ADM assays and RNA-seq; JNK-AP1/JUND phosphoregulation in skin tumorigenesis

    PMID:36261000 PMID:37270580

    Open questions at the time
    • Molecular determinant switching iASPP between oncogenic and suppressive output not identified
    • Relationship to its p53-inhibitory function in these tissues unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how the multiple post-translational switches and competing partner pools are coordinated to assign iASPP to a specific function in a given cell state.
  • No unified model relating phosphorylation, cleavage, and localization to partner choice
  • Full PP1 substrate repertoire targeted by iASPP undefined
  • Structural basis of non-p53 inhibitory complexes lacking

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 6 GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 1
Localization
GO:0005634 nucleus 5 GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 2 GO:0005829 cytosol 2
Pathway
R-HSA-1640170 Cell Cycle 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 3
Partners
CEP55DSPKEAP1MAPRE1PPP1CARELATP53VHL
Complex memberships
desmosome/intercalated disciASPP-PP1 complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 iASPP (encoded by PPP1R13L) is an evolutionarily conserved inhibitor of p53; inhibition of iASPP by RNA-mediated interference or antisense RNA in C. elegans or human cells induces p53-dependent apoptosis. iASPP cooperates with Ras, E1A, and E7 (but not mutant p53) to transform cells in vitro, establishing it as an oncoproteein that suppresses p53-mediated apoptosis. RNA interference in C. elegans and antisense RNA in human cells; oncogenic cooperation/transformation assays in vitro Nature genetics High 12524540
2006 iASPP binds to the proline-rich region (PRR) of p53 in addition to the DNA-binding domain. iASPP preferentially binds and inhibits the p53Pro72 variant over p53Arg72, providing a mechanism by which p53Arg72 activates apoptosis more efficiently. Binding assays between ASPP family members and p53 PRR; functional apoptosis assays with p53 codon 72 polymorphic variants Nature genetics High 16964264
2004 iASPP exists as a longer isoform (828 aa) with an N-terminal extension that is predominantly cytoplasmic, causing the full-length iASPP to localize to both cytoplasm and nucleus, whereas the shorter iASPP(RAI) is predominantly nuclear. The N-terminus of iASPP is required for cytoplasmic localization. Both isoforms bind p53 and inhibit p53-induced apoptosis. Subcellular fractionation, immunofluorescence, reporter assays; p53 binding and apoptosis inhibition assays Oncogene High 15489900
2007 Pin1 (prolyl isomerase) mediates dissociation of p53 from the apoptosis inhibitor iASPP after phosphorylation of p53 at Ser46 by cytotoxic stimuli, thereby promoting p53-dependent cell death. Pin1 is required for efficient p53 loading onto target promoters and stimulates p300-mediated p53 acetylation. Co-immunoprecipitation, chromatin immunoprecipitation, reporter assays, mutagenesis of Pin1-binding residues Nature structural & molecular biology High 17906639
2011 iASPP interacts with PP1 (protein phosphatase 1) via a noncanonical RNYF motif located within its SH3 domain, distinct from the canonical RVXF motif used by ASPP2. Phe-815 is critical for iASPP/PP1 interaction; iASPP(F815A) fails to inhibit p53 transcriptional and apoptotic function. Co-immunoprecipitation, GST pulldown, site-directed mutagenesis (F815A), functional p53 apoptosis assays The Journal of biological chemistry High 21998301
2011 iASPP is a binding partner and negative regulator of p65RelA (NF-κB subunit) as well as p53. In stratified epithelia, nuclear iASPP co-localizes with p63 in basal keratinocytes; iASPP binds p63 and inhibits transcriptional activity of both TAp63α and ΔNp63α, regulating epithelial stratification and preventing premature senescence in mouse embryonic fibroblasts. Transgenic mouse (Cre/loxP iASPP knockout), Co-IP, reporter assays, in vivo keratinocyte differentiation assays, immunofluorescence co-localization Proceedings of the National Academy of Sciences of the United States of America High 21930934
2011 iASPP promotes resistance to paclitaxel by reducing mitotic catastrophe in a p53-independent manner via activation of separase, with both securin and cyclin B1/CDK1 complex involved in regulating separase activity downstream of iASPP. iASPP overexpression and knockdown in ovarian cancer cells; functional mitotic catastrophe, apoptosis, and separase activity assays Clinical cancer research Medium 21926165
2013 Cyclin B1/CDK1 phosphorylates iASPP, leading to inhibition of iASPP dimerization, promotion of iASPP monomer nuclear entry, and exposure of its p53-binding sites, resulting in increased p53 inhibition. Phosphorylated nuclear iASPP is enriched in melanoma metastasis. Phosphorylation assays, dimerization assays, nuclear fractionation, small-molecule CDK1 inhibition, co-immunoprecipitation; crystal structure data cited for binding sites Cancer cell High 23623661
2012 iASPP inhibits p53-independent apoptosis by inhibiting the transcriptional activity of p63 and p73 on promoters of proapoptotic genes. Reporter assays for p63/p73 transcriptional activity; iASPP knockdown/overexpression; apoptosis assays in p53-deficient tumor cells Apoptosis Medium 22538442
2015 iASPP interacts with desmoplakin and desmin in cardiomyocytes to maintain the integrity of desmosomes and intermediate filament networks. iASPP deficiency induces right ventricular dilatation and causes ARVC-like sudden cardiac death in mice. ARVC-derived desmoplakin mutants (DSP-1-V30M and DSP-1-S299R) show weaker binding to iASPP. Co-immunoprecipitation, iASPP knockout mouse model (Ppp1r13lΔ8/Δ8), in vitro desmosome integrity assays, immunofluorescence at intercalated discs, human ARVC tissue analysis Proceedings of the National Academy of Sciences of the United States of America High 25691752
2017 iASPP competes with Nrf2 for Keap1 binding via a DLT motif, leading to decreased Nrf2 ubiquitination, increased Nrf2 accumulation, nuclear translocation, and antioxidative transactivation. This iASPP-Keap1-Nrf2 axis promotes cancer growth and drug resistance independently of p53. Co-immunoprecipitation, competitive binding assays, ubiquitination assays, Nrf2 nuclear translocation assays, DLT motif mutagenesis; in vitro and in vivo tumor growth assays Cancer cell High 29033244
2014 iASPP acts as an autophagy inhibitor in keratinocytes by specifically reducing the interaction of Atg5-Atg12 with Atg16L1, an interaction essential for autophagosome formation or maturation. iASPP depletion activates autophagy and modulates mTORC1 signaling and mitochondrial dynamics. iASPP siRNA knockdown, LC3 lipidation assay, Co-IP of Atg5-Atg12/Atg16L1 complex, organotypic culture differentiation assay, mitochondrial imaging Journal of cell science Medium 24777476
2015 iASPP stabilizes p300 and CBP (histone acetyltransferases) by interfering with BRMS1-mediated ubiquitination of p300/CBP, thereby contributing to apoptotic susceptibility via TAp73-dependent transcription of pro-apoptotic genes. Co-immunoprecipitation, iASPP shRNA knockdown, ubiquitination assays, reporter assays for TAp73 target promoters, apoptosis assays upon cisplatin treatment Cell death & disease Medium 25675294
2015 Caspase cleaves the N-terminal region of iASPP at SSLD294 upon apoptotic stimuli, generating an 80 kDa fragment that translocates from cytoplasm to nucleus via the RaDAR nuclear import pathway (independent of p53). This 80 kDa fragment binds and inhibits p53 or RelA/p65 more efficiently than full-length iASPP. Caspase cleavage assays, site identification by mutagenesis (SSLD294), subcellular fractionation, nuclear import pathway analysis, Co-IP with p53 and RelA/p65 Oncotarget Medium 26646590
2018 iASPP acts as a PP1-targeting subunit (regulatory subunit) to facilitate interaction between PP1 and CEP55, promoting dephosphorylation of PLK1-mediated Ser436 phosphorylation in CEP55 during late mitosis, which is required for timely CEP55 recruitment to the midbody. iASPP depletion causes abnormal midbody structure and failed cytokinesis. Protein affinity purification, Co-IP, iASPP depletion with cytokinesis phenotype assays, phosphorylation assays for CEP55-Ser436 Cell death & disease High 29743530
2019 Crystal structure of the p53-iASPP complex reveals that iASPP displaces the p53 L1 loop (which mediates sequence-specific DNA interactions) without perturbing other DNA-recognizing modules of the p53 DNA-binding domain. iASPP modulates p53 DNA-binding site selectivity through this mechanism. The iASPP binding surface overlaps with the HPV E6 footprint on p53, distinct from other p53-binding tumor suppressors/oncoproteins. X-ray crystallography (crystal structure of p53-iASPP complex); genome-wide p53 binding site sequence analysis; functional validation of selectivity Proceedings of the National Academy of Sciences of the United States of America High 31395738
2018 iASPP physically interacts with CD44 standard isoform (CD44s) via the ankyrin-binding domain of CD44s. Hyaluronan stimulation promotes formation of iASPP-CD44s complexes in fibroblasts. CD44 alters subcellular localization of the iASPP-p53 complex; ablation of CD44 promotes translocation of iASPP from nucleus to cytoplasm, increasing cytoplasmic iASPP-p53 complex formation. iASPP is required for hyaluronan-induced CD44-dependent fibroblast migration. Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, migration/adhesion assays Cancers Medium 36831425
2017 PPP1R13L (iASPP) directly inhibits the transcriptional activity of SP1 via protein-protein interaction. SP1 in turn transcriptionally activates PPP1R13L expression, forming a feedback loop that regulates nicotine-induced epithelial-mesenchymal transition in lung cancer cells. Co-immunoprecipitation demonstrating iASPP-SP1 protein interaction; reporter assays; EMT cell model with nicotine treatment Biochemical pharmacology Medium 36372331
2022 iASPP suppresses Gp78-mediated ubiquitination and degradation of TMCO1 (a Ca2+-channel protein) by competitively binding with Gp78, thereby reducing ER Ca2+ stores and modulating Ca2+ homeostasis. This iASPP-TMCO1 axis promotes tumor growth and drug resistance. Co-immunoprecipitation, competitive binding assays, ubiquitination assays at K186 of TMCO1, Ca2+ measurement assays, in vitro and in vivo tumor growth assays Proceedings of the National Academy of Sciences of the United States of America High 35121659
2022 iASPP directly binds VHL at its β domain (which also binds HIF-1α), blocking VHL-mediated ubiquitination and degradation of HIF-1α under normoxia. This stabilizes HIF-1α and promotes angiogenesis and glycolysis in cancer cells. Co-immunoprecipitation, competitive binding assays between iASPP, VHL, and HIF-1α, iASPP genetic inhibition with HIF-1α protein level measurement, in vivo tumor growth assays Oncogene High 35169254
2022 During prolonged ER stress, iASPP mRNA stabilization by HuR is impaired, reducing iASPP protein. iASPP competes with GRP78 for binding the ER-resident E3 ligase RNF185; when iASPP levels fall, GRP78 is degraded by RNF185, facilitating transition to terminal UPR and cell death. Co-immunoprecipitation (iASPP vs GRP78 competition for RNF185), iASPP knockdown/overexpression with GRP78 stability assays, HuR mRNA stabilization assays Cell death and differentiation Medium 36380064
2017 PPP1R13L loss-of-function (homozygous stop codon) causes a cardio-cutaneous syndrome in humans. In patient fibroblasts and iASPP-deficient cardiomyocytes, the NF-κB-dependent inflammatory response to LPS is hypersensitive; iASPP normally dampens NF-κB binding activity at promoters of pro-inflammatory cytokine genes. Human genetics (identifying PPP1R13L premature stop codon), NF-κB EMSA and ChIP on patient fibroblasts, siRNA knockdown of Ppp1r13l in murine cardiomyocytes, RNA sequencing of Ppp1r13l-deficient mouse hearts EMBO molecular medicine High 28069640
2018 In cardiomyocyte-specific iASPP-deficient mice, loss of iASPP is sufficient to cause cardiac disorder; in keratinocyte-specific iASPP-deficient mice, loss of iASPP causes cutaneous disorder, delayed eyelid development, and impaired wound healing. Junctional iASPP in keratinocytes is critical for desmosome stabilization; its deficiency results in increased and disorganized cell migration and impaired cell adhesion. Cardiomyocyte-specific and keratinocyte-specific Cre/loxP iASPP knockout mice, desmosome integrity assays, cell migration and adhesion assays, wound healing models Cell death and differentiation High 29352264
2009 Overexpression of PPP1R13L promotes p53 degradation via the proteasome, depletes active p65/RelA, and accelerates tumor formation driven by RAS/E1A, modulating both p53-dependent and p53-independent apoptosis pathways. Overexpression in primary MEFs (with/without p53); proteasome inhibitor (MG132) experiments; in vivo tumor formation assays Molecular carcinogenesis Medium 19263435
2015 iASPP is identified as an ERK-primed GSK-3 substrate; in the presence of GSK-3, iASPP is targeted for degradation, linking KSHV LANA-mediated kinase dysregulation to iASPP stability. Protein microarray phosphorylation screen, cotransfection with GSK-3, proteasome-dependent degradation assay Journal of virology Medium 26109723
2017 CDK1 (cyclin-dependent kinase 1) physically interacts with iASPP protein; this interaction affects colorectal cancer cell proliferation and apoptosis through the p53 apoptosis pathway. GST pulldown assay, Co-immunoprecipitation, cell proliferation and apoptosis assays with CDK1 and iASPP manipulations Oncotarget Medium 29069733
2021 iASPP associates with the microtubule plus-end binding protein EB1 via an SxIP motif, and with Myosin-Ic (Myo1c). iASPP loss or mutation of its SxIP motif leads to defective microtubule capture at the cortex of mitotic cells, abnormal mitotic spindle positioning, and failure of cells to round up during mitosis due to defective cortical stiffness. Co-immunoprecipitation, SxIP motif mutagenesis, iASPP and Myo1c siRNA knockdown, atomic force microscopy for cortical stiffness, live imaging of mitotic spindle The Journal of cell biology High 34705028
2022 JNK-mediated phosphorylation of iASPP inhibits iASPP binding with AP1 components (such as JUND) via PXXP/SH3 domain-mediated interaction. iASPP regulates expression of a subset of p63 and AP1 target genes involved in skin differentiation and inflammation, acting as a tumor suppressor in RAS-driven, inflammation-promoted skin tumorigenesis. JNK phosphorylation assays, Co-IP of iASPP with JUND, iASPP loss-of-function in RAS/inflammation-driven mouse skin tumor model, gene expression profiling Cell reports Medium 36261000
2023 iASPP suppresses KRAS-driven and inflammation-driven pancreatic cancer tumorigenesis and acinar-to-ductal metaplasia in a p53-independent manner; transcriptomic analysis shows iASPP deletion and p53 mutation overlap extensively in NF-κB and AP1-regulated inflammatory gene sets. Genetic mouse models (KRASG12D with iASPPΔ8/Δ8), in vitro ADM assays, syngeneic/nude mouse tumor models, RNA sequencing Cell death and differentiation High 37270580
2018 iASPP interacts with NAF-1 (a NEET 2Fe-2S protein); peptide mapping and computational analysis localized the interaction to residues 764-778 of iASPP binding a surface groove of NAF-1. This iASPP-NAF-1 interaction is stimulated during apoptosis in cancer cells and is required for apoptosis activation. Peptide array screening, computational modeling, cell-based interaction assay, apoptosis inhibition assay with iASPP 764-780 peptide in cancer cells Chemical science Medium 30774867
2021 Measles virus C protein specifically interacts with the p65-iASPP protein complex, as determined by affinity purification/mass spectrometry and protein complementation assay, potentially hijacking the cell death and innate immunity regulatory functions of this complex. Affinity purification coupled to mass spectrometry, protein complementation assay (PCA), bioluminescence resonance energy transfer (BRET) Molecular & cellular proteomics Medium 33515806
2020 iASPP inhibits chemotherapy-induced senescence (TIS) by translocating to the nucleus in senescent cells (driven by NF-κBp65 transcriptional induction), where it binds p53 and NF-κBp65, inhibiting their transcriptional activation of p21 and SASP factors IL-6/IL-8, thereby preventing senescence and conferring drug resistance independently of apoptosis. iASPP knockdown in HCT116 and MCF-7 cells, xenograft model, Co-IP of iASPP with p53 and p65, reporter assays, senescence markers (SA-β-Gal, p21) The Journal of biological chemistry Medium 32005663
2017 FHL2 is a binding partner of iASPP (identified by yeast two-hybrid screen and confirmed by Co-IP); FHL2 and iASPP co-localize in both nucleus and cytoplasm of leukemia cells. When FHL2 is knocked down, iASPP protein expression also decreases, and vice versa, suggesting mutual stabilization. Yeast two-hybrid screen, Co-immunoprecipitation, immunofluorescence co-localization, siRNA knockdown, Western blot Oncotarget Medium 28402264
2010 NF-κB increases expression of iASPP through p65/p50 binding to a putative NF-κB-binding site in the iASPP promoter; hepatitis B virus X protein upregulates iASPP expression via NF-κB activation. Luciferase reporter assay, chromatin immunoprecipitation, electrophoretic mobility shift assay (EMSA) Gastroenterology High 20600029
2010 p53 and PPP1R13L form a negative feedback loop: p53 accumulation after DNA damage drives PPP1R13L expression (dependent on p53 target genes BAX and GADD45α), while PPP1R13L in turn inhibits p53 function. Proteasome inhibition leads to accumulation of both p53 and PPP1R13L. siRNA knockdown of p53, PPP1R13L, BAX, and GADD45α; Western blot, qPCR, proteasome inhibitor (MG132) treatment in human and mouse cells with varying p53 status Biochimica et biophysica acta Medium 20840860
2014 iASPP phosphorylation at serine residues (which increases iASPP affinity toward p53) is significantly reduced following optic nerve axotomy in retinal ganglion cells (RGCs). iASPP knockdown exacerbates RGC death after axotomy; AAV-mediated iASPP overexpression promotes RGC survival and downregulates p53 activity and pro-apoptotic targets PUMA and Fas/CD95. siRNA knockdown, AAV-mediated overexpression, in vivo optic nerve axotomy model, phospho-specific Western blot, p53 target gene expression analysis PloS one Medium 24714389

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human. Nature genetics 317 12524540
2006 iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72-polymorphic p53. Nature genetics 218 16964264
2017 iASPP Is an Antioxidative Factor and Drives Cancer Growth and Drug Resistance by Competing with Nrf2 for Keap1 Binding. Cancer cell 165 29033244
2007 The prolyl isomerase Pin1 orchestrates p53 acetylation and dissociation from the apoptosis inhibitor iASPP. Nature structural & molecular biology 134 17906639
2013 Restoring p53 function in human melanoma cells by inhibiting MDM2 and cyclin B1/CDK1-phosphorylated nuclear iASPP. Cancer cell 132 23623661
2011 iASPP/p63 autoregulatory feedback loop is required for the homeostasis of stratified epithelia. The EMBO journal 85 21897369
2005 The expression of iASPP in acute leukemias. Leukemia research 81 15607367
2016 The lncRNA H19 interacts with miR-140 to modulate glioma growth by targeting iASPP. Archives of biochemistry and biophysics 76 27693036
2017 The lncRNA UCA1 interacts with miR-182 to modulate glioma proliferation and migration by targeting iASPP. Archives of biochemistry and biophysics 74 28137422
2017 iASPP induces EMT and cisplatin resistance in human cervical cancer through miR-20a-FBXL5/BTG3 signaling. Journal of experimental & clinical cancer research : CR 71 28399926
2011 iASPP and chemoresistance in ovarian cancers: effects on paclitaxel-mediated mitotic catastrophe. Clinical cancer research : an official journal of the American Association for Cancer Research 68 21926165
2016 Long noncoding RNA MALAT1-regulated microRNA 506 modulates ovarian cancer growth by targeting iASPP. OncoTargets and therapy 63 28031721
2010 iASPP is over-expressed in human non-small cell lung cancer and regulates the proliferation of lung cancer cells through a p53 associated pathway. BMC cancer 61 21192816
2013 MicroRNA-124 regulates the proliferation of colorectal cancer cells by targeting iASPP. BioMed research international 58 23691514
2011 Inhibitor of apoptosis-stimulating protein of p53 (iASPP) prevents senescence and is required for epithelial stratification. Proceedings of the National Academy of Sciences of the United States of America 54 21930934
2004 The N-terminus of a novel isoform of human iASPP is required for its cytoplasmic localization. Oncogene 54 15489900
2017 lncRNA XIST interacts with miR-140 to modulate lung cancer growth by targeting iASPP. Oncology reports 51 28656261
2013 Downregulation of miR-124 promotes the growth and invasiveness of glioblastoma cells involving upregulation of PPP1R13L. International journal of molecular medicine 46 23624869
2010 Increased expression of iASPP, regulated by hepatitis B virus X protein-mediated NF-κB activation, in hepatocellular carcinoma. Gastroenterology 44 20600029
2010 RNA interference-mediated silencing of iASPP induces cell proliferation inhibition and G0/G1 cell cycle arrest in U251 human glioblastoma cells. Molecular and cellular biochemistry 43 21184255
2020 Increases of iASPP-Keap1 interaction mediated by syringin enhance synaptic plasticity and rescue cognitive impairments via stabilizing Nrf2 in Alzheimer's models. Redox biology 42 32828017
2014 iASPP is a novel autophagy inhibitor in keratinocytes. Journal of cell science 42 24777476
2015 ASPP and iASPP: Implication in cancer development and progression. Cellular and molecular biology (Noisy-le-Grand, France) 40 26518890
2010 Genetic polymorphisms in ATM, ERCC1, APE1 and iASPP genes and lung cancer risk in a population of southeast China. Medical oncology (Northwood, London, England) 40 20354815
2015 iASPP, a previously unidentified regulator of desmosomes, prevents arrhythmogenic right ventricular cardiomyopathy (ARVC)-induced sudden death. Proceedings of the National Academy of Sciences of the United States of America 39 25691752
2012 iASPP inhibits p53-independent apoptosis by inhibiting transcriptional activity of p63/p73 on promoters of proapoptotic genes. Apoptosis : an international journal on programmed cell death 38 22538442
2017 Wild-type and mutant p53 differentially modulate miR-124/iASPP feedback following pohotodynamic therapy in human colon cancer cell line. Cell death & disease 37 29022915
2015 HEDGEHOG/GLI-E2F1 axis modulates iASPP expression and function and regulates melanoma cell growth. Cell death and differentiation 37 26024388
2008 iASPP inhibition: increased options in targeting the p53 family for cancer therapy. Cancer research 35 18593889
2008 Effect of RNA interference of iASPP on the apoptosis in MCF-7 breast cancer cells. Cancer investigation 34 18798069
2014 Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is required for neuronal survival after axonal injury. PloS one 32 24714389
2017 CDK1 interacts with iASPP to regulate colorectal cancer cell proliferation through p53 pathway. Oncotarget 31 29069733
2017 The lncRNA XIST interacts with miR-140/miR-124/iASPP axis to promote pancreatic carcinoma growth. Oncotarget 31 29371940
2022 iASPP suppresses Gp78-mediated TMCO1 degradation to maintain Ca2+ homeostasis and control tumor growth and drug resistance. Proceedings of the National Academy of Sciences of the United States of America 30 35121659
2014 Nuclear iASPP may facilitate prostate cancer progression. Cell death & disease 29 25341046
2012 Elevated expression of iASPP in head and neck squamous cell carcinoma and its clinical significance. Medical oncology (Northwood, London, England) 29 22815155
2018 Impact of iASPP on chemoresistance through PLK1 and autophagy in ovarian clear cell carcinoma. International journal of cancer 28 29663364
2016 MicroRNA-182 aggravates cerebral ischemia injury by targeting inhibitory member of the ASPP family (iASPP). Archives of biochemistry and biophysics 28 27242323
2019 iASPP mediates p53 selectivity through a modular mechanism fine-tuning DNA recognition. Proceedings of the National Academy of Sciences of the United States of America 27 31395738
2011 Down-regulation of iASPP in human hepatocellular carcinoma cells inhibits cell proliferation and tumor growth. Neoplasma 27 21391736
2011 Inhibitory member of the apoptosis-stimulating proteins of the p53 family (iASPP) interacts with protein phosphatase 1 via a noncanonical binding motif. The Journal of biological chemistry 27 21998301
2008 Linkage disequilibrium mapping of a breast cancer susceptibility locus near RAI/PPP1R13L/iASPP. BMC medical genetics 27 18588689
2016 A novel all-trans retinoic acid derivative 4-amino‑2‑trifluoromethyl-phenyl retinate inhibits the proliferation of human hepatocellular carcinoma HepG2 cells by inducing G0/G1 cell cycle arrest and apoptosis via upregulation of p53 and ASPP1 and downregulation of iASPP. Oncology reports 26 27177208
2016 Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of microRNA-124. Scientific reports 26 27765948
2019 CDK9 inhibitors reactivate p53 by downregulating iASPP. Cellular signalling 25 31866490
2018 Mild Therapeutic Hypothermia Protects the Brain from Ischemia/Reperfusion Injury through Upregulation of iASPP. Aging and disease 25 29896428
2015 Reactivating p53 functions by suppressing its novel inhibitor iASPP: a potential therapeutic opportunity in p53 wild-type tumors. Oncotarget 24 26343523
2011 iASPP is important for bladder cancer cell proliferation. Oncology research 24 21473288
2009 siRNA-mediated down-regulation of iASPP promotes apoptosis induced by etoposide and daunorubicin in leukemia cells expressing wild-type p53. Leukemia research 24 19299014
2017 Sequence variation in PPP1R13L results in a novel form of cardio-cutaneous syndrome. EMBO molecular medicine 23 28069640
2017 iASPP facilitates tumor growth by promoting mTOR-dependent autophagy in human non-small-cell lung cancer. Cell death & disease 23 29072696
2014 Oncogene iASPP enhances self-renewal of hematopoietic stem cells and facilitates their resistance to chemotherapy and irradiation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 24668753
2009 Enforced expression of PPP1R13L increases tumorigenesis and invasion through p53-dependent and p53-independent mechanisms. Molecular carcinogenesis 22 19263435
2022 Blocking iASPP/Nrf2/M-CSF axis improves anti-cancer effect of chemotherapy-induced senescence by attenuating M2 polarization. Cell death & disease 20 35190529
2018 Cell autonomous role of iASPP deficiency in causing cardiocutaneous disorders. Cell death and differentiation 20 29352264
2016 MicroRNA-140 regulates cell growth and invasion in pancreatic duct adenocarcinoma by targeting iASPP. Acta biochimica et biophysica Sinica 20 26787707
2014 MicroRNA124 regulate cell growth of prostate cancer cells by targeting iASPP. International journal of clinical and experimental pathology 20 24966937
2012 Abnormal expression pattern of the ASPP family of proteins in human non-small cell lung cancer and regulatory functions on apoptosis through p53 by iASPP. Oncology reports 20 22552744
2012 Waved with open eyelids 2 (woe2) is a novel spontaneous mouse mutation in the protein phosphatase 1, regulatory (inhibitor) subunit 13 like (Ppp1r13l) gene. BMC genetics 19 22928477
2022 iASPP suppression mediates terminal UPR and improves BRAF-inhibitor sensitivity of colon cancers. Cell death and differentiation 18 36380064
2015 Caspase cleavage of iASPP potentiates its ability to inhibit p53 and NF-κB. Oncotarget 18 26646590
2007 Identification of a novel isoform of iASPP and its interaction with p53. Journal of molecular biology 18 17391696
2020 LncRNA XIST Promotes Growth of Human Chordoma Cells by Regulating miR-124-3p/iASPP Pathway. OncoTargets and therapy 17 32547104
2019 Epigenetic Regulation of iASPP-p63 Feedback Loop in Cutaneous Squamous Cell Carcinoma. The Journal of investigative dermatology 17 30710576
2017 iASPP, a microRNA‑124 target, is aberrantly expressed in astrocytoma and regulates malignant glioma cell migration and viability. Molecular medicine reports 17 29257240
2018 iASPP-PP1 complex is required for cytokinetic abscission by controlling CEP55 dephosphorylation. Cell death & disease 16 29743530
2013 Helicobacter pylori infection and expressions of apoptosis-related proteins p53, ASPP2 and iASPP in gastric cancer and precancerous lesions. Pathologie-biologie 16 23528480
2022 iASPP is essential for HIF-1α stabilization to promote angiogenesis and glycolysis via attenuating VHL-mediated protein degradation. Oncogene 15 35169254
2020 A previously identified apoptosis inhibitor iASPP confers resistance to chemotherapeutic drugs by suppressing senescence in cancer cells. The Journal of biological chemistry 15 32005663
2018 MicroRNA-150 inhibits the proliferation and metastasis potential of colorectal cancer cells by targeting iASPP. Oncology reports 15 29750311
2017 MicroRNA-184 Modulates Human Central Nervous System Lymphoma Cells Growth and Invasion by Targeting iASPP. Journal of cellular biochemistry 15 28012196
2015 Association and interaction of NFKB1 rs28362491 insertion/deletion ATTG polymorphism and PPP1R13L and CD3EAP related to lung cancer risk in a Chinese population. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 15 26563375
2023 Common variants of pro-inflammatory gene IL1B and interactions with PPP1R13L and POLR1G in relation to lung cancer among Northeast Chinese. Scientific reports 14 37147350
2022 Transcription factor SP1 and oncoprotein PPP1R13L regulate nicotine-induced epithelial-mesenchymal transition in lung adenocarcinoma via a feedback loop. Biochemical pharmacology 14 36372331
2020 Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy. Clinical genetics 14 32666529
2018 MiR-340/iASPP axis affects UVB-mediated retinal pigment epithelium (RPE) cell damage. Journal of photochemistry and photobiology. B, Biology 14 29982095
2015 A pro-apoptotic function of iASPP by stabilizing p300 and CBP through inhibition of BRMS1 E3 ubiquitin ligase activity. Cell death & disease 14 25675294
2022 Mutant Ras and inflammation-driven skin tumorigenesis is suppressed via a JNK-iASPP-AP1 axis. Cell reports 12 36261000
2018 The anti-apoptotic proteins NAF-1 and iASPP interact to drive apoptosis in cancer cells. Chemical science 12 30774867
2010 p53 and PPP1R13L (alias iASPP or RAI) form a feedback loop to regulate genotoxic stress responses. Biochimica et biophysica acta 12 20840860
2021 iASPP contributes to cell cortex rigidity, mitotic cell rounding, and spindle positioning. The Journal of cell biology 11 34705028
2020 iASPP-Mediated ROS Inhibition Drives 5-Fu Resistance Dependent on Nrf2 Antioxidative Signaling Pathway in Gastric Adenocarcinoma. Digestive diseases and sciences 11 31938994
2023 Hyaluronan-Induced CD44-iASPP Interaction Affects Fibroblast Migration and Survival. Cancers 10 36831425
2018 Different splicing isoforms of ERCC1 affect the expression of its overlapping genes CD3EAP and PPP1R13L, and indicate a potential application in non-small cell lung cancer treatment. International journal of oncology 10 29620255
2018 GLTSCR1, ATM, PPP1R13L and CD3EAP Genetic Variants and Lung Cancer Risk in a Chinese Population. Current medical science 10 30128886
2015 A Screen for Extracellular Signal-Regulated Kinase-Primed Glycogen Synthase Kinase 3 Substrates Identifies the p53 Inhibitor iASPP. Journal of virology 10 26109723
2023 Regulation of immunological tolerance by the p53-inhibitor iASPP. Cell death & disease 9 36746936
2021 Malignant transformation of human bronchial epithelial cells induced by benzo [a] pyrene suggests a negative feedback of TP53 to PPP1R13L via binding a possible enhancer element. Chemico-biological interactions 9 34610339
2017 iASPP overexpression is associated with clinical outcome in spinal chordoma and influences cellular proliferation, invasion, and sensitivity to cisplatin in vitro. Oncotarget 9 28978123
2023 p53 inhibitor iASPP is an unexpected suppressor of KRAS and inflammation-driven pancreatic cancer. Cell death and differentiation 8 37270580
2021 Proteomic Analysis Uncovers Measles Virus Protein C Interaction With p65-iASPP Protein Complex. Molecular & cellular proteomics : MCP 8 33515806
2017 19p13.3-GADD45B common variants and 19q13.3-PPP1R13L and 19q13.3-CD3EAP in lung cancer risk among Chinese. Chemico-biological interactions 8 28870783
2014 A small peptide derived from p53 linker region can resume the apoptotic activity of p53 by sequestering iASPP with p53. Cancer letters 8 25444901
2013 Effects of PPP1R13L and CD3EAP variants on lung cancer susceptibility among nonsmoking Chinese women. Gene 8 23624123
2021 Nuclear iASPP determines cell fate by selectively inhibiting either p53 or NF-κB. Cell death discovery 7 34312379
2019 Overexpression of iASPP is required for autophagy in response to oxidative stress in choriocarcinoma. BMC cancer 7 31615473
2017 FHL2 interacts with iASPP and impacts the biological functions of leukemia cells. Oncotarget 7 28402264
2015 NFKB1 common variants and PPP1R13L and CD3EAP in relation to lung cancer risk in a Chinese population. Gene 7 25917613
2022 Novel homozygous stop-gain pathogenic variant of PPP1R13L gene leads to arrhythmogenic cardiomyopathy. BMC cardiovascular disorders 6 35933355
2018 miR-129 targets CDK1 and iASPP to modulate Burkitt lymphoma cell proliferation in a TAp63-dependent manner. Journal of cellular biochemistry 6 30105797

Missed literature

Know a paper Affinage missed for PPP1R13L? Flag it for the maintainers and the community.

No submissions yet.