Affinage

PIAS4

E3 SUMO-protein ligase PIAS4 · UniProt Q8N2W9

Length
510 aa
Mass
56.5 kDa
Annotated
2026-06-10
85 papers in source corpus 47 papers cited in narrative 47 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

PIAS4 (PIASy) is a nuclear SUMO E3 ligase that uses an SP-RING/RING-finger catalytic core, two C-terminal SUMO-interacting motifs, and an N-terminal SAP domain to conjugate SUMO1 or SUMO2/3 to a broad panel of nuclear substrates, thereby controlling transcription factor output, genome maintenance, mitotic chromosome dynamics, and metabolic and stress signaling (PMID:11731474, PMID:15933717, PMID:28455449). As a transcriptional regulator it predominantly represses its targets, SUMOylating LEF1/Tcf, C/EBPalpha, GATA-2, c-Myb, p53, Smad3, YY1, and others to alter their localization, DNA binding, stability, or coactivator access—for example sequestering LEF1 and c-Myb into the nuclear matrix and driving SUMO-dependent nuclear export of Smad3 (PMID:11731474, PMID:12511558, PMID:12631292, PMID:18384750); in several contexts it represses transcription factors (AR, C/EBPdelta, LRH-1) through ligase-independent mechanisms involving HDAC recruitment, SAP-domain-mediated nuclear sequestration, or coactivator competition (PMID:14981544, PMID:18477566, PMID:19067654). In the DNA damage response PIAS4 is recruited to double-strand breaks via its SAP domain to deposit SUMO1, enabling productive 53BP1/BRCA1/RNF168 recruitment and RNF8/RNF168/BRCA1 ubiquitin signaling, and it drives end resection and template-switch tolerance through SUMOylation of substrates including PCNA-Lys164 and RIF1 (PMID:20016603, PMID:29234018, PMID:30487218, PMID:35007836). During mitosis PIAS4 localizes to centromeres via the Rod/Zw10 complex and catalyzes SUMO2/3 modification of Topoisomerase IIalpha and PARP1 on chromosomes, an activity essential for sister chromatid segregation (PMID:15933717, PMID:21079245, PMID:20228053, PMID:20696768). PIAS4 additionally governs senescence and apoptosis via p53/Rb (PMID:16793547), NF-kappaB and type I/II interferon signaling (PMID:16906147, PMID:17606919, PMID:21199872), hypoxia responses through HIF1alpha and VHL SUMOylation (PMID:20300531, PMID:20661221), and AMPK/mTORC1 and hepatic lipogenic control via AMPKalpha1 and SREBP1c SUMOylation (PMID:24379443, PMID:26616021). Its own abundance and activity are tuned by autologous SUMO1 modification at Lys35 and by TRIM32- and FIEL1-mediated ubiquitination and proteasomal degradation (PMID:15831457, PMID:16816390, PMID:27162139). Single PIAS4-knockout mice are largely normal, but Pias1/Pias4 double knockouts are embryonic lethal, establishing extensive functional redundancy within the PIAS family (PMID:15169916, PMID:15528356, PMID:17606919).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2001 High

    Established PIAS4 as a bona fide SUMO E3 ligase and transcriptional repressor, defining its core biochemical activity and a sequestration-based repression mode.

    Evidence Reconstituted in vitro ligase assay, in vivo sumoylation, and nuclear-body/matrix localization for LEF1; reciprocal Co-IP and reporter assays for p53

    PMID:11388671 PMID:11731474

    Open questions at the time
    • Did not define the catalytic determinants of ligase activity
    • Mechanism linking nuclear-matrix sequestration to repression not resolved at structural level
  2. 2003 High

    Showed PIAS4 SUMOylates and represses multiple developmental and signaling transcription factors, embedding it in TGF-beta/Smad and hematopoietic transcription networks, sometimes via HDAC recruitment.

    Evidence In vitro and in vivo sumoylation, yeast two/three-hybrid, Co-IP, reporter and EMSA assays for C/EBPalpha, Smad3/4/7, GATA-2, and c-Myb

    PMID:12511558 PMID:12631292 PMID:12750312 PMID:12815042 PMID:12904571

    Open questions at the time
    • Did not distinguish ligase-dependent from ligase-independent repression for all substrates
    • In vivo relevance of feedback induction by TGF-beta not tested genetically
  3. 2004 High

    Demonstrated a SUMO-ligase-independent repression mechanism via HDAC recruitment and showed in vivo that PIAS4 is dispensable at steady state but contributes modestly to STAT1/Wnt outputs.

    Evidence Domain/ligase-dead mutants and HDAC inhibitor for AR repression; knockout mice with 2D-gel SUMO proteome and signaling assays

    PMID:14981544 PMID:15169916 PMID:15528356

    Open questions at the time
    • Source of in vivo redundancy (which PIAS paralog compensates) not mapped
    • Did not reconcile strong in vitro activities with mild knockout phenotype
  4. 2005 High

    Defined PIAS4 as the dedicated mitotic chromosomal SUMO2/3 ligase whose activity is essential for sister chromatid segregation, and showed autologous SUMO1 modification at Lys35 tunes substrate-selective output.

    Evidence Xenopus egg extract depletion/rescue with Ubc9 recruitment and segregation readouts; site-directed mutagenesis (K35R) with sumoylation, localization, and Tcf-4 reporter assays

    PMID:15831457 PMID:15933717

    Open questions at the time
    • Full set of mitotic chromosomal substrates not yet enumerated
    • How K35 SUMOylation rewires substrate selectivity mechanistically unresolved
  5. 2006 High

    Connected PIAS4 to genotoxic NF-kappaB activation, p53/Rb-driven senescence and apoptosis, and identified TRIM32-mediated ubiquitination as a degradation switch controlling PIAS4 levels.

    Evidence In vitro sumoylation/ubiquitination with purified components, siRNA, Co-IP, ChIP, ligase-dead mutants, and patient fibroblasts for NEMO, p53/Rb, and TRIM32

    PMID:16793547 PMID:16816390 PMID:16906147

    Open questions at the time
    • Stimulus specificity of nuclear PIAS4-NEMO interaction not fully defined
    • Physiological triggers of TRIM32-PIAS4 redistribution beyond UVB/TNFalpha unclear
  6. 2007 High

    Revealed RING-independent substrate SUMOylation (YY1) and established cooperative, partially redundant control of NF-kappaB/STAT1 gene programs with PIAS1, including essential developmental function.

    Evidence In vitro/in vivo sumoylation and stability assays for YY1; single and double knockout mice with dendritic-cell gene expression and embryonic lethality

    PMID:17353273 PMID:17606919

    Open questions at the time
    • Basis for RING-independent SUMO transfer not structurally explained
    • Distinct vs overlapping target sets of PIAS1 and PIAS4 incompletely resolved
  7. 2008 Medium

    Defined mechanisms by which PIAS4 controls transcription factor localization: SUMO-driven Smad3 nuclear export and SAP-domain-mediated nuclear-periphery sequestration of C/EBPdelta; linked PIAS4 to FIP200/mTOR signaling.

    Evidence siRNA, FRET, nuclear export and DNA-binding assays for Smad3; domain mutants and immunofluorescence for C/EBPdelta; Co-IP, fractionation, ChIP for FIP200

    PMID:18285457 PMID:18384750 PMID:18477566

    Open questions at the time
    • Whether export and sequestration mechanisms operate on shared substrates untested
    • FIP200-PIAS4 functional consequences in vivo not established
  8. 2009 High

    Placed PIAS4 at the apex of double-strand-break SUMO signaling and showed coactivator-competition as a distinct repression mode.

    Evidence Irradiation-induced foci imaging, SAP-domain mutants, repair and clonogenic survival assays (with PIAS1); Co-IP and competition assays for LRH-1

    PMID:19067654 PMID:20016603

    Open questions at the time
    • Direct SUMO substrates driving 53BP1/BRCA1/RNF168 recruitment not all identified at DSBs
    • Recruitment cue read by the SAP domain at breaks undefined
  9. 2010 High

    Expanded the PIAS4 substrate repertoire across mitosis, hypoxia, and DNA-gate enzymology, defining site-specific modifications with direct functional consequences.

    Evidence Mass spectrometry site mapping, in vitro decatenation and PARP assays, Xenopus extracts, Co-IP, siRNA, and angiogenesis/growth assays for TopoIIalpha-K660, PARP1-K482, HIF1alpha, VHL-K171; Rod/Zw10 domain mapping for centromeric targeting

    PMID:20228053 PMID:20300531 PMID:20661221 PMID:20696768 PMID:21079245

    Open questions at the time
    • How a single ligase achieves substrate- and site-selectivity across these targets unresolved
    • Opposing HIF1alpha (destabilizing) vs VHL (inactivating) effects not integrated into one model
  10. 2011 High

    Dissected two ligase-independent interferon-restriction mechanisms of PIAS4 acting through SIM/UBC9 and the SAP-domain LXXLL motif.

    Evidence PIAS4-null cells with ligase-dead, LXXLL, SIM, and UBC9-knockdown reporter assays

    PMID:21199872

    Open questions at the time
    • Molecular targets of the SIM-dependent and LXXLL-dependent repression not identified
    • In vivo antiviral relevance not tested here
  11. 2013 Medium

    Identified a hypoxia-induced PIAS4-Sp1-SIRT1 transcriptional repression axis driving EMT and metastasis, and a SREBP1c-SUMOylation node suppressing hepatic lipogenesis.

    Evidence siRNA, ChIP, in vivo sumoylation, xenograft metastasis for Sp1/SIRT1; mutagenesis, Co-IP, db/db and lean mouse studies, primary hepatocytes for SREBP1c-K98

    PMID:23843607 PMID:24379443

    Open questions at the time
    • Direct vs indirect contribution of Sp1 SUMOylation to SIRT1 promoter occupancy not fully isolated
    • Upstream signals coupling PKA to PIAS4-SREBP1c beyond PKA activation incompletely defined
  12. 2015 High

    Established PIAS4 as the AMPKalpha1 SUMO ligase that selectively restrains AMPK signaling toward mTORC1, linking it to growth control and a cancer vulnerability.

    Evidence In vivo sumoylation, ligase-dead PIAS4 and SUMO-deficient AMPKalpha1 reconstitution in knockout cells, mTORC1 and cell growth assays

    PMID:26616021

    Open questions at the time
    • SUMO acceptor site on AMPKalpha1 and structural basis of pathway selectivity not defined
    • Generality across AMPK complexes/tissues untested
  13. 2016 High

    Revealed a phosphorylation-gated FIEL1 ubiquitination switch controlling PIAS4 turnover and TGF-beta/fibrosis, and embedded PIAS4 in SUMO-targeted ubiquitin cascades and viral restriction.

    Evidence In vitro ubiquitination, phosphorylation assays, bleomycin model and inhibitor for FIEL1; Co-IP/sumoylation/ChIP for E12, SIRT1-SMAD3, Nkx3.2-RNF4; viral replication and SIM-mutant analysis for HSV-1

    PMID:22829926 PMID:26937035 PMID:27162139 PMID:27312341 PMID:27323886

    Open questions at the time
    • Interplay between TRIM32 and FIEL1 degradation pathways not reconciled
    • Whether SUMO-targeted RNF4 ubiquitination acts on the same PIAS4-modified substrate pools broadly unclear
  14. 2017 High

    Defined structural and pathway determinants of PIAS4 activity: a second C-terminal SIM required for full ligase function, and PIAS4-driven control of RIF1 and Rbp2/KDM5B-mediated chromatin/IFN regulation.

    Evidence NMR chemical-shift mapping and in vitro activity for SIMs; siRNA, Co-IP, sumoylation/ubiquitination for RIF1; Co-IP, ChIP, enzyme-dead mutant for Rbp2

    PMID:28455449 PMID:28970247 PMID:29234018

    Open questions at the time
    • How the two SIMs cooperate with the SP-RING during catalysis structurally unresolved
    • Direct vs scaffolding role of PIAS4 in the RIF1-UHRF1 turnover circuit incompletely separated
  15. 2018 High

    Demonstrated genetically that PIAS1/PIAS4 jointly drive PCNA-Lys164 SUMOylation to enable the template-switch DNA damage tolerance pathway.

    Evidence DT40 and TK6 double-knockouts, PCNA-SUMO1 chimera rescue, Ig gene conversion, and epistasis analysis

    PMID:30487218

    Open questions at the time
    • Relative contribution of PIAS1 vs PIAS4 to PCNA SUMOylation not separated
    • Coupling of PCNA SUMOylation to downstream recombinase choice not detailed
  16. 2019 Medium

    Implicated PIAS4 SUMOylation in early embryonic gene-expression control, restraining the 2C-like program via DPPA2 and constraining chromatin state and chromosome segregation in zygotes.

    Evidence Depletion/overexpression with in vivo sumoylation, ESC-to-2C transition and early embryo assays for DPPA2; embryo microinjection, segregation and H3K9me3 readouts with ligase-dead mutant

    PMID:31226106 PMID:31640975

    Open questions at the time
    • Direct functional consequence of DPPA2-SUMO on its targets not mapped
    • Link between PIAS4 SUMO activity and H3K9me3 methyltransferase translocation mechanistic detail lacking
  17. 2021 Medium

    Refined the DSB role of PIAS4 to promoting end resection and RAD51 loading by counteracting the 53BP1/RIF1 resection blockade within a PIAS1/PIAS4/RNF4/BRCA1 module.

    Evidence siRNA, gamma-irradiation DSB-marker imaging, and epistasis (53BP1 depletion rescue)

    PMID:35007836

    Open questions at the time
    • Direct SUMO substrate driving resection licensing not pinpointed
    • Order of action relative to RNF4 in this module not fully resolved
  18. 2022 Medium

    Extended PIAS4 SUMO signaling to cardiac membrane biology, where Cav-3 SUMO2/3 modification disrupts Nav1.5 channel localization and promotes ischemia-reperfusion arrhythmias.

    Evidence AAV9-shRNA cardiac knockdown, Co-IP, Cav-3 SUMO-site mutants, ECG, and hypoxia/reoxygenation cell model

    PMID:36229865

    Open questions at the time
    • Whether Cav-3 SUMOylation is direct PIAS4 catalysis vs indirect not fully isolated
    • Generalizability beyond the I/R context untested
  19. 2024 Medium

    Linked PIAS4-RNF4 SUMO-targeted degradation to extraction of trapped WRN helicase and uncovered a transcriptional regulator-controlled PIAS4-SLC7A11 ferroptosis axis as cancer vulnerabilities.

    Evidence Single-molecule tracking, phenotypic screens, inhibitor/siRNA and MSI-H xenografts for WRN; pull-down, Co-IP, ChIP, luciferase and xenograft models for SLC7A11/KDM1A

    PMID:38615741 PMID:39025847

    Open questions at the time
    • Direct PIAS4 substrate at trapped-WRN chromatin not biochemically defined
    • Whether SLC7A11 SUMOylation site and degradation pathway are universal across tumors unclear
  20. 2025 Low

    Began characterizing oxidative-stress-induced TDP-43 SUMOylation by PIAS4, hinting at a stress-specific role with possible neurodegeneration relevance.

    Evidence In vivo sumoylation assay under oxidative stress with domain mapping and PIAS1/PIAS4 co-expression (preprint)

    PMID:41292941

    Open questions at the time
    • Preprint, single lab, no mechanistic follow-up
    • Functional consequence of TDP-43 SUMOylation undefined
    • Stimulus specificity (oxidative vs DNA-damage) basis unexplained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single ligase achieves substrate- and site-selectivity across its many targets, and how its catalytic (SP-RING/SIM) versus ligase-independent (SAP/HDAC/coactivator-competition) modes are partitioned in vivo, remain unresolved.
  • No structure of PIAS4 engaging a substrate-SUMO-Ubc9 complex
  • Rules governing SUMO1 vs SUMO2/3 paralog choice across substrates unknown
  • Tissue-specific contributions vs PIAS-family redundancy not systematically mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 7 GO:0140096 catalytic activity, acting on a protein 7 GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 2
Localization
GO:0000228 nuclear chromosome 4 GO:0005634 nucleus 4 GO:0005654 nucleoplasm 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-392499 Metabolism of proteins 7 R-HSA-74160 Gene expression (Transcription) 6 R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-1640170 Cell Cycle 4 R-HSA-73894 DNA Repair 4 R-HSA-8953897 Cellular responses to stimuli 3
Partners
FIEL1HDAC1NEMOPIAS1RIF1RNF4TRIM32UBC9

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 PIASy (PIAS4) functions as a SUMO E3 ligase for LEF1 in a reconstituted in vitro system, stimulates LEF1 sumoylation in vivo, and represses LEF1 transcriptional activity by sequestering it into nuclear bodies via binding to nuclear matrix-associated DNA sequences. Reconstituted in vitro SUMO E3 ligase assay, co-expression sumoylation assay, nuclear body localization by immunofluorescence, nuclear matrix binding assay Genes & development High 11731474
2001 PIASy (PIAS4) interacts with p53 (confirmed by yeast two-hybrid and co-immunoprecipitation in mammalian cells), inhibits p53 DNA-binding activity and p53-dependent transactivation of Bax and p21, but does not suppress p53-induced apoptosis. Yeast two-hybrid, co-immunoprecipitation, luciferase reporter assay, EMSA Apoptosis Medium 11388671
2003 PIASy (PIAS4) acts as a SUMO E3 ligase for C/EBPalpha, enhancing both SUMO-1 and SUMO-3 modification at the synergy control (SC) motif (Lys159) both in vivo and in vitro; SUMO modification at this site suppresses transcriptional synergy from compound response elements. In vitro SUMOylation assay with purified recombinant components, in vivo sumoylation assay, site-directed mutagenesis, reporter gene assay The Journal of biological chemistry High 12511558
2003 PIASy (PIAS4) interacts with Smad3 and Smad4 (identified by yeast three-hybrid screen, confirmed in mammalian cells); the interaction with Smad3 is enhanced by TGF-beta and occurs through the C-terminal domain of Smad3. PIASy represses Smad transcriptional activity without inhibiting Smad-DNA binding, and can interact constitutively with HDAC1; HDAC inhibitor TSA prevents PIASy's inhibitory function. Yeast three-hybrid screen, co-immunoprecipitation, reporter gene assay, EMSA, HDAC inhibitor experiment Proceedings of the National Academy of Sciences of the United States of America High 12815042 12904571
2003 PIASy (PIAS4) stimulates sumoylation of Smad3 in vivo and associates with Smad7 (identified by yeast two-hybrid with Smad7 MH2 domain as bait); endogenous PIASy expression is induced by TGF-beta in Hep3B cells, suggesting a negative feedback loop. Yeast two-hybrid, co-immunoprecipitation, in vivo sumoylation assay The Journal of biological chemistry Medium 12815042
2003 PIASy (PIAS4) interacts with GATA-2, preferentially enhances SUMO-2 conjugation to GATA-2 via its E3 SUMO ligase activity, and suppresses GATA-2-dependent ET-1 promoter activity in endothelial cells through a RING-like domain-independent mechanism requiring both N-terminal and C-terminal sequences of PIASy. Co-immunoprecipitation, in vivo sumoylation assay, reporter gene assay, domain deletion analysis Circulation research Medium 12750312
2003 PIASy (PIAS4) is a SUMO E3 ligase for c-Myb, enhancing SUMO-1 conjugation at K503 and K527 both in vitro and in vivo; PIASy causes a shift of c-Myb to the insoluble nuclear matrix fraction and negatively regulates Myb-induced transcriptional activation. In vitro SUMOylation assay, co-immunoprecipitation, reporter gene assay, nuclear fractionation, site-directed mutagenesis European journal of biochemistry Medium 12631292
2004 PIASy (PIAS4) represses androgen receptor (AR) transcriptional activity by recruiting HDAC1 and HDAC2 via its RD1 repression domain; HDAC activity is required for this repression. The repression is independent of PIASy's SUMO ligase activity and independent of AR sumoylation status. Co-immunoprecipitation, reporter gene assay, HDAC inhibitor experiment, domain deletion and SUMO-ligase-dead mutant analysis Oncogene High 14981544
2004 PIASy (PIAS4) knockout mice are phenotypically normal with no significant perturbation of STAT1 activation or global SUMO-1/SUMO-3 modification patterns, demonstrating that PIASy is either dispensable or compensated by other PIAS family members at steady state. Knockout mouse generation, 2D gel analysis of SUMO-modified proteins, STAT1 activation assay Molecular and cellular biology High 15169916 15528356
2004 PIASy (PIAS4) deletion in mice results in modest reduction of IFN-gamma-induced and Wnt-responsive gene expression, demonstrating partial but non-essential roles in STAT1 and LEF1 signaling with likely redundancy from other PIAS family members. Knockout mouse, gene expression analysis, signaling assays in primary cells Journal of immunology High 15528356
2005 PIASy (PIAS4) is specifically required for mitotic SUMO-2 conjugation of Topoisomerase-II in Xenopus egg extracts; PIASy binds mitotic chromosomes and recruits Ubc9 to chromatin, and these properties are essential for its activity. PIASy depletion eliminates chromosomal SUMO-2-conjugated species and blocks anaphase sister chromatid segregation. Xenopus egg extract depletion, immunofluorescence, EGFP-SUMO-2 localization, functional segregation assay, dominant-negative mutant analysis The EMBO journal High 15933717
2005 SUMO-1 modification of PIASy itself at Lys35 is required for PIASy-dependent sumoylation and transcriptional activation of Tcf-4; PIASy(K35R) retains ligase activity for other substrates but loses the ability to activate Tcf-4, correlating with distinct nuclear distribution including increased PML body association. Site-directed mutagenesis, in vivo sumoylation assay, reporter gene assay, immunofluorescence, co-immunoprecipitation Molecular and cellular biology Medium 15831457
2006 PIASy (PIAS4) is the SUMO E3 ligase for NEMO (IKKgamma), preferentially stimulating site-selective SUMO-1 (but not SUMO-2/3) modification of NEMO in vitro; PIASy-NEMO interaction is increased by genotoxic stress and occurs in the nucleus, mutually exclusive with IKK interaction. PIASy siRNA inhibits NEMO sumoylation and NF-kappaB activation in response to genotoxic agents. siRNA knockdown, in vitro SUMOylation assay, co-immunoprecipitation, overexpression, subcellular fractionation Nature cell biology High 16906147
2006 PIASy (PIAS4) overexpression in normal human fibroblasts induces cellular senescence via the p53 and Rb tumor suppressor pathways; in Rb-deficient fibroblasts, PIASy expression leads to p53-dependent apoptosis. PIASy stimulates sumoylation and transcriptional activity of p53 and increases Rb-dependent corepression at E2F-responsive promoters. Fibroblasts lacking PIASy exhibit reduced senescence in response to prosenescence stimuli. Senescence induction requires PIASy E3 ligase activity. Overexpression in primary fibroblasts, PIASy knockout cells, E3-ligase-dead mutant, in vivo sumoylation assay, ChIP, reporter gene assay Molecular cell High 16793547
2006 TRIM32 interacts with PIASy (PIAS4), promotes PIASy ubiquitination and proteasomal degradation in vitro using purified components; this interaction is induced by UVB/TNFalpha treatment and involves redistribution of PIASy from the nucleus to cytoplasmic granules. The LGMD2H-associated TRIM32 missense mutation prevents TRIM32-PIASy interaction. PIASy inhibits NF-kappaB activity and sensitizes keratinocytes to apoptosis; TRIM32-mediated PIASy degradation thus regulates NF-kappaB-dependent survival. In vitro ubiquitination assay with purified components, co-immunoprecipitation, immunofluorescence, NF-kappaB reporter assay, patient fibroblasts The Journal of biological chemistry High 16816390
2007 PIASy (PIAS4) is a SUMO E3 ligase for YY1, stimulating YY1 sumoylation at Lys288 in vitro and in vivo; uniquely, PIASy-mediated YY1 sumoylation does not depend on the RING finger domain of PIASy but correlates with PIASy-YY1 interaction. PIASy colocalizes with YY1 in the nucleus, stabilizes YY1 protein, and differentially regulates YY1 transcriptional activity on different target promoters. In vitro and in vivo sumoylation assay, site-directed mutagenesis, co-immunoprecipitation, immunofluorescence, reporter gene assay, stability assay Molecular and cellular biology High 17353273
2007 PIASy (PIAS4) and PIAS1 cooperate to regulate specificity and magnitude of NF-kappaB and STAT1-mediated gene activation; Piasy deletion in dendritic cells enhances a subset of NF-kappaB and STAT1 target genes, and Pias1-/-Piasy-/- double knockout embryos die before day 11.5, demonstrating essential cooperative function. Single and double knockout mice, gene expression analysis in primary dendritic cells, endotoxic shock model Proceedings of the National Academy of Sciences of the United States of America High 17606919
2008 PIASy (PIAS4) sumoylation of Smad3 stimulates Smad3 nuclear export; co-expression of Smad3 with PIASy and SUMO1 affected Smad3 DNA-binding activity and promoted nuclear export. FRET analysis revealed Smad3 interacts with SUMO1 in the cytoplasm. siRNA-mediated reduction of endogenous PIASy enhanced TGF-beta-induced gene expression. siRNA knockdown, nuclear export assay, FRET analysis, DNA-binding assay, reporter gene assay Biochemical and biophysical research communications Medium 18384750
2008 PIASy (PIAS4) represses C/EBPdelta transcriptional activity by sequestering it to the nuclear periphery via interaction between the PIASy SAP domain (SAPD) and the C/EBPdelta transactivation domain (TAD); this repression is independent of HDAC activity, PIASy E3 SUMO ligase activity, and C/EBPdelta sumoylation. Domain deletion analysis, reporter gene assay, HDAC inhibitor experiment, immunofluorescence, SUMO-ligase-dead mutant The Journal of biological chemistry Medium 18477566
2008 FIP200 interacts with PIASy (PIAS4) via the PIASy RING finger and FIP200 C-terminus; PIASy interaction redistributes FIP200 from cytoplasm to nucleus, abrogating FIP200 regulation of TSC/S6K signaling. FIP200 enhances PIASy-dependent transcriptional activation of the p21 promoter; both proteins are co-recruited to the p21 promoter by ChIP. FIP200 is not a SUMO substrate of PIASy. Co-immunoprecipitation, in vitro/in vivo sumoylation assay, immunofluorescence, subcellular fractionation, ChIP, siRNA knockdown, reporter gene assay Molecular and cellular biology Medium 18285457
2009 PIAS4 and PIAS1 are recruited to DNA double-strand break sites via SAP domain-dependent mechanisms; PIAS4 is required for SUMO1 accumulation and PIAS1 for SUMO2/3 accumulation at DSB sites. Both are needed for productive association of 53BP1, BRCA1, and RNF168 with damage foci, and for effective ubiquitin-adduct formation by RNF8, RNF168, and BRCA1. Both promote DSB repair and confer ionizing radiation resistance. Immunofluorescence of irradiation-induced foci, siRNA knockdown, domain mutant analysis, DSB repair assay, clonogenic survival assay Nature High 20016603
2009 PIASy (PIAS4) inhibits LRH-1-mediated transactivation by competing with the co-activator SRC-1 for binding to the LRH-1 AF-2 domain; this repression is independent of LRH-1 SUMOylation and HDAC activity. Co-immunoprecipitation, mammalian two-hybrid, reporter gene assay, domain deletion analysis, overexpression competition assay The Biochemical journal Medium 19067654
2010 PIASy (PIAS4) interacts with VHL and induces VHL SUMOylation at Lys171 by SUMO1; PIASy-mediated SUMOylation promotes VHL oligomerization and abrogates its inhibitory function on tumor cell growth, migration, and clonogenicity. PIASy siRNA reduces VHL oligomerization and increases HIF1alpha degradation. PIASy is upregulated under hypoxic conditions. Co-immunoprecipitation, in vivo sumoylation assay, site-directed mutagenesis, siRNA knockdown, cell growth/migration assay, ubiquitination assay PloS one Medium 20300531
2010 PIASy (PIAS4) is a specific E3 ligase for hypoxia-induced HIF1alpha SUMOylation by SUMO1; hypoxia promotes nuclear translocation of HIF1alpha to enable PIASy binding. PIASy negatively regulates hypoxia-induced HIF1alpha stability and transactivation; PIASy knockdown increases angiogenic activity of endothelial cells. Co-immunoprecipitation, in vivo sumoylation assay, siRNA knockdown, reporter gene assay, angiogenesis assay (tube formation), immunofluorescence Oncogene Medium 20661221
2010 PIASy (PIAS4)-mediated SUMO2/3 modification of Topoisomerase IIalpha at Lys660 (in the DNA gate domain) strongly inhibits TopoIIalpha decatenation activity; loss of SUMOylation at Lys660 eliminates this inhibitory effect. The SUMOylation site was identified by mass spectrometry. Mass spectrometry, biochemical decatenation assay, site-directed mutagenesis, Xenopus egg extract sumoylation assay The Journal of cell biology High 21079245
2010 PIASy (PIAS4) promotes SUMO-2/3 conjugation of PARP1 at Lys482 (identified by tandem mass spectrometry) on mitotic chromosomes but not interphase chromatin, both in Xenopus egg extracts and in vitro reconstituted assays. PARP1 SUMOylation does not alter intrinsic PARP1 enzymatic activity or its localization on chromosomes, but loss of SUMOylation increases PARP1-dependent PARylation of other chromatin-associated proteins. Xenopus egg extract SUMOylation, tandem mass spectrometry, in vitro reconstituted SUMOylation assay, site-directed mutagenesis, PARP enzymatic activity assay The Journal of biological chemistry High 20228053
2010 The Rod/Zw10 kinetochore complex interacts with the N-terminal domain of PIASy (PIAS4) (specifically first 47 residues) and is required for PIASy centromeric localization and mitotic SUMO2/3 conjugation on chromosomes; Rod depletion compromises centromeric localization of PIASy and SUMO2/3. Xenopus egg extract depletion, co-immunoprecipitation, immunofluorescence, domain truncation analysis, N-terminal domain swapping The Journal of biological chemistry High 20696768
2011 PIASy (PIAS4) inhibits virus-induced type I IFN transcription through a SUMO E3-ligase-independent mechanism requiring SUMO-interacting motif (SIM) activity and UBC9; PIASy inhibits IFN-stimulated gene expression through its SAP domain LXXLL motif. These two inhibitory mechanisms are distinct: LXXLL mutation abolishes IFN-stimulated gene repression but not virus-induced IFN transcription. PIASy null mouse cells, overexpression, SUMO-ligase-dead mutant, LXXLL motif mutant, SIM mutant, UBC9 knockdown, reporter gene assay The Journal of biological chemistry High 21199872
2013 PIASy (PIAS4) is induced by hypoxia and promotes SUMOylation of Sp1, preventing Sp1 from binding to the SIRT1 promoter and thereby transcriptionally repressing SIRT1 expression; PIASy knockdown restores Sp1 binding and SIRT1 expression, reverses cancer cell EMT, and attenuates metastasis in vivo in nude mice. siRNA knockdown, ChIP, in vivo sumoylation assay, EMT markers, in vivo xenograft metastasis assay Journal of cell science Medium 23843607
2013 PIASy (PIAS4) sumoylates SREBP1c at Lys98, leading to suppression of the hepatic lipogenic program; PKA activation enhances PIASy-SREBP1c interaction and SREBP1c sumoylation, followed by ubiquitination-dependent degradation. PIASy overexpression in db/db mice ameliorates hepatic steatosis; PIASy suppression in lean mice stimulates lipogenesis. In vivo sumoylation assay, site-directed mutagenesis, co-immunoprecipitation, in vivo mouse studies (db/db and WT), primary hepatocyte experiments, PKA activation assay Molecular and cellular biology High 24379443
2015 PIAS4 and its SUMO E3 ligase activity are specifically required for SUMOylation of AMPKalpha1, which attenuates AMPK activity specifically towards mTORC1 signaling. SUMOylation-deficient AMPKalpha1 shows higher activity towards mTORC1 when reconstituted in AMPKalpha-deficient cells. PIAS4 depletion reduces breast cancer cell growth specifically when combined with AMPK activator A769662. In vivo SUMOylation assay, SUMO-ligase-dead PIAS4 mutant, SUMOylation-deficient AMPKalpha1 reconstitution in knockout cells, mTORC1 signaling assay, cell growth assay Nature communications High 26616021
2016 FIEL1 (KIAA0317) ubiquitinates PIAS4 in a site-specific manner facilitated by PKCzeta phosphorylation of PIAS4 and GSK3beta phosphorylation of FIEL1 (double-locking mechanism), leading to PIAS4 degradation and enhancement of TGF-beta signaling. FIEL1 overexpression increases lung fibrosis in a bleomycin model; a FIEL1 small molecule inhibitor ameliorates fibrosis. Co-immunoprecipitation, in vitro ubiquitination assay, phosphorylation assays, bleomycin murine fibrosis model, small molecule inhibitor The Journal of experimental medicine High 27162139
2016 PIAS4 acts as SUMO E3 ligase for E12 (a class I bHLH protein) in vivo; PIASy RING mutant cannot block E12-mediated alpha-SMA promoter activation, indicating RING domain is required for E12 sumoylation; TGF-beta induces both PIASy and E12 expression; reduced PIASy expression leads to increased TGF-beta-mediated alpha-SMA expression in mesangial cells. In vivo sumoylation assay, yeast two-hybrid, co-immunoprecipitation, reporter gene assay, RING domain mutant, siRNA knockdown PloS one Medium 22829926
2016 PIAS4 promotes HSC activation and liver fibrosis by transcriptionally repressing SIRT1, which leads to SMAD3 hyperacetylation and enhanced SMAD3 binding to fibrogenic gene promoters; lentivirus-shRNA targeting PIAS4 in mice ameliorates liver fibrosis by normalizing SIRT1 expression. shRNA knockdown in vivo (lentivirus), ChIP, gene expression analysis, in vivo mouse model (MCD diet) Scientific reports Medium 27323886
2016 PIAS4 is recruited to nuclear domains containing HSV-1 viral DNA via SUMO-interacting motif (SIM)-dependent mechanisms (at viral genome entry sites) and via SIM-independent mechanisms (in replication compartments). PIAS4 depletion enhances replication of ICP0-null HSV-1; its restriction mechanisms are synergistic with PML protein and antagonized by ICP0. Immunofluorescence co-localization, siRNA depletion, viral replication assay, SIM mutant analysis Journal of virology Medium 26937035
2016 HDAC9 deacetylation of Nkx3.2 triggers PIASy (PIAS4)-mediated sumoylation of Nkx3.2, and subsequent RNF4-mediated SUMO-targeted ubiquitination; this HDAC9-PIASy-RNF4 post-translational cascade controls Nkx3.2 protein stability and regulates chondrocyte hypertrophy and viability during skeletal development. Co-immunoprecipitation, in vivo sumoylation and ubiquitination assays, HDAC inhibitor, chondrocyte differentiation assay Cellular signalling Medium 27312341
2017 PIAS4 is the primary SUMO E3 ligase for RIF1 SUMOylation in response to DNA damage; PIAS4 knockdown impairs RIF1 SUMOylation, defective disassembly of RIF1 DDR foci, and abrogates UHRF1-dependent ubiquitination and turnover of RIF1, leading to accumulated RIF1 at damage sites and DNA double-strand breaks. siRNA knockdown, co-immunoprecipitation, immunofluorescence, in vivo sumoylation assay, ubiquitination assay Scientific reports Medium 29234018
2017 PIASy (PIAS4) contains two SUMO-interacting motifs (SIMs) at its C-terminus; both are required for full E3 ligase activity. The new SIM was identified by NMR chemical shift mapping and validated by mutagenesis. NMR chemical shift mapping, mutagenesis, in vitro SUMOylation assay The Journal of biological chemistry High 28455449
2018 PIAS1 and PIAS4 together promote SUMO-dependent template switch (TS) DNA damage tolerance pathway by SUMOylating PCNA at Lys164; PIAS1/PIAS4 double-knockout cells show >90% decrease in PCNA-Lys164 SUMOylation and >90% decrease in TS (Ig gene conversion). Epistasis experiments show PCNA mutation causes no additional impact on PIAS1/PIAS4 cells; overexpression of PCNA-SUMO1 chimera restores TS in PIAS1/PIAS4 cells. Genetic knockout (chicken DT40 and human TK6 cells), PCNA-SUMO1 chimera reconstitution, Ig gene conversion assay, epistasis analysis Proceedings of the National Academy of Sciences of the United States of America High 30487218
2018 PIASy (PIAS4) interacts with Rbp2 (KDM5B/JARID1A histone H3K4me3 demethylase) via the PIASy PINIT domain (101-218 aa) and the Rbp2 JmjC domain (451-503 aa); Piasy binds the IFN-beta promoter and facilitates Rbp2-mediated demethylation of H3K4me3 at IFNI genes, attenuating type I IFN transcription. Enzymatically inactive Rbp2 does not attenuate IFNI. Co-immunoprecipitation, ChIP, domain deletion analysis, siRNA/shRNA knockdown, enzymatically inactive mutant (Rbp2H483G/E485Q), reporter gene assay FASEB journal Medium 28970247
2019 PIAS4 sumoylates DPPA2 protein, negatively regulating its activity; PIAS4 is down-regulated during zygotic genome activation (ZGA). Depleting Pias4 or overexpressing Dppa2/4 is sufficient to activate 2C-like transcriptional program; forced expression of Pias4 or Sumo2-DPPA2 fusion inhibits 2C-like program and impairs early mouse embryo development. siRNA/shRNA depletion, overexpression, in vivo sumoylation assay, ESC-to-2C-like cell transition model, early embryo development assay PLoS biology Medium 31226106
2019 PIASy (PIAS4) overexpression in fertilized mouse embryos causes developmental arrest at the two-cell stage with abnormal chromosome segregation and impaired zygotic transcription; this is dependent on PIASy SUMOylation activity and associated with increased H3K9me3 trimethylation and enhanced nuclear translocation of H3K9me3 methyltransferase. mRNA microinjection/overexpression in embryos, chromosome segregation analysis, H3K9me3 immunofluorescence, SUMO-ligase-dead mutant Biology open Medium 31640975
2021 PIAS4 depletion impairs DSB end resection and RAD51 loading in gamma-ray-irradiated human fibroblasts, reducing BRCA1 recruitment to DSB sites; 53BP1 depletion rescues resection in PIAS4-depleted cells. Epistasis analysis shows PIAS4, PIAS1, RNF4, and BRCA1 work epistatically to counteract 53BP1/RIF1-mediated resection blockade. siRNA depletion, gamma-ray irradiation, immunofluorescence of DSB markers, epistasis analysis Biochemical and biophysical research communications Medium 35007836
2022 PIASy (PIAS4)-mediated SUMOylation of Caveolin-3 (Cav-3) by SUMO2/3 increases after myocardial ischemia-reperfusion (I/R); increased Cav-3 SUMOylation causes Nav1.5/Cav-3 dissociation, reducing membrane Nav1.5 density; cardiac-targeted PIASy silencing decreases Cav-3 SUMO2/3 modification, restores Nav1.5-Cav-3 co-localization, and prevents I/R-induced ventricular arrhythmias in rats. AAV9-shRNA in vivo cardiac knockdown, co-immunoprecipitation, site-directed mutagenesis of Cav-3 SUMO sites, immunofluorescence, ECG recording, HEK293T hypoxia/reoxygenation model Military Medical Research Medium 36229865
2024 WRN helicase inhibition traps WRN on chromatin, requiring SUMOylation via the PIAS4-RNF4 axis for subsequent p97/VCP-mediated extraction and proteasomal degradation; co-inhibition of WRN and SUMOylation has additive toxicity in MSI-H cancer cells. Single-molecule tracking (SMT), phenotypic screen, siRNA/inhibitor studies, co-inhibition experiments, in vivo MSI-H xenograft model Nature communications Medium 39025847
2024 PIAS4 directly binds SLC7A11 and facilitates its SUMOylation; KDM1A acts as a transcriptional activator of PIAS4. Tanshinone IIA decreases KDM1A expression, suppressing PIAS4 transcription and thereby inhibiting PIAS4-dependent SLC7A11 SUMOylation, which promotes SLC7A11 degradation and ferroptosis in breast cancer cells. Ni-beads pull-down, co-immunoprecipitation, luciferase assay, ChIP, siRNA knockdown, in vivo xenograft and metastasis models Journal of advanced research Medium 38615741
2025 PIAS4 facilitates SUMOylation of TDP-43 by SUMO1 and SUMO2/3 in response to oxidative stress; PIAS1 also contributes. TDP-43 SUMOylation is not promoted by etoposide-induced DNA damage. In vivo sumoylation assay, oxidative stress treatment, domain mapping, PIAS1/PIAS4 co-expression bioRxivpreprint Low 41292941

Source papers

Stage 0 corpus · 85 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes & development 457 11731474
2009 Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks. Nature 441 20016603
2006 PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress. Nature cell biology 185 16906147
2006 The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis. Molecular cell 144 16793547
2003 A synergy control motif within the attenuator domain of CCAAT/enhancer-binding protein alpha inhibits transcriptional synergy through its PIASy-enhanced modification by SUMO-1 or SUMO-3. The Journal of biological chemistry 126 12511558
2005 PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes. The EMBO journal 123 15933717
2003 Repression of Smad transcriptional activity by PIASy, an inhibitor of activated STAT. Proceedings of the National Academy of Sciences of the United States of America 94 12904571
2019 DPPA2/4 and SUMO E3 ligase PIAS4 opposingly regulate zygotic transcriptional program. PLoS biology 82 31226106
2013 PIASy mediates hypoxia-induced SIRT1 transcriptional repression and epithelial-to-mesenchymal transition in ovarian cancer cells. Journal of cell science 77 23843607
2004 Protein inhibitor of activated STAT Y (PIASy) and a splice variant lacking exon 6 enhance sumoylation but are not essential for embryogenesis and adult life. Molecular and cellular biology 76 15169916
2007 PIASy-mediated sumoylation of Yin Yang 1 depends on their interaction but not the RING finger. Molecular and cellular biology 75 17353273
2006 The interaction of Piasy with Trim32, an E3-ubiquitin ligase mutated in limb-girdle muscular dystrophy type 2H, promotes Piasy degradation and regulates UVB-induced keratinocyte apoptosis through NFkappaB. The Journal of biological chemistry 75 16816390
2003 Regulation of transforming growth factor-beta signaling by protein inhibitor of activated STAT, PIASy through Smad3. The Journal of biological chemistry 75 12815042
2010 Hypoxia inactivates the VHL tumor suppressor through PIASy-mediated SUMO modification. PloS one 73 20300531
2007 Control of specificity and magnitude of NF-kappa B and STAT1-mediated gene activation through PIASy and PIAS1 cooperation. Proceedings of the National Academy of Sciences of the United States of America 72 17606919
2004 PIASy-mediated repression of the androgen receptor is independent of sumoylation. Oncogene 71 14981544
2004 PIASy-deficient mice display modest defects in IFN and Wnt signaling. Journal of immunology (Baltimore, Md. : 1950) 69 15528356
2010 PIASy stimulates HIF1α SUMOylation and negatively regulates HIF1α activity in response to hypoxia. Oncogene 64 20661221
2010 PIASy-dependent SUMOylation regulates DNA topoisomerase IIalpha activity. The Journal of cell biology 63 21079245
2003 Transactivation properties of c-Myb are critically dependent on two SUMO-1 acceptor sites that are conjugated in a PIASy enhanced manner. European journal of biochemistry 62 12631292
2001 A putative protein inhibitor of activated STAT (PIASy) interacts with p53 and inhibits p53-mediated transactivation but not apoptosis. Apoptosis : an international journal on programmed cell death 57 11388671
2003 Modification of GATA-2 transcriptional activity in endothelial cells by the SUMO E3 ligase PIASy. Circulation research 56 12750312
2010 Regulation of the psoriatic chemokine CCL20 by E3 ligases Trim32 and Piasy in keratinocytes. The Journal of investigative dermatology 54 20054338
2010 PIASy mediates SUMO-2/3 conjugation of poly(ADP-ribose) polymerase 1 (PARP1) on mitotic chromosomes. The Journal of biological chemistry 51 20228053
2013 PIASy-mediated sumoylation of SREBP1c regulates hepatic lipid metabolism upon fasting signaling. Molecular and cellular biology 50 24379443
2008 Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-beta signaling. Biochemical and biophysical research communications 50 18384750
2005 SUMO-1 modification of PIASy, an E3 ligase, is necessary for PIASy-dependent activation of Tcf-4. Molecular and cellular biology 50 15831457
2005 Interactions between coilin and PIASy partially link Cajal bodies to PML bodies. Journal of cell science 48 16219678
2011 mRNA expression of BRCA1, PIAS1, and PIAS4 and survival after second-line docetaxel in advanced gastric cancer. Journal of the National Cancer Institute 47 21862729
2006 Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection. Journal of virology 42 16352559
2013 PIAS4 is an activator of hypoxia signalling via VHL suppression during growth of pancreatic cancer cells. British journal of cancer 40 24002598
2015 SUMOylation of AMPKα1 by PIAS4 specifically regulates mTORC1 signalling. Nature communications 39 26616021
2004 PIASy represses TRIF-induced ISRE and NF-kappaB activation but not apoptosis. FEBS letters 38 15251447
2024 Tanshinone IIA destabilizes SLC7A11 by regulating PIAS4-mediated SUMOylation of SLC7A11 through KDM1A, and promotes ferroptosis in breast cancer. Journal of advanced research 37 38615741
2012 Characterization of a PIAS4 homologue from zebrafish: insights into its conserved negative regulatory mechanism in the TRIF, MAVS, and IFN signaling pathways during vertebrate evolution. Journal of immunology (Baltimore, Md. : 1950) 36 22345667
2016 Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response. Journal of virology 35 26937035
2018 SUMOylation of PCNA by PIAS1 and PIAS4 promotes template switch in the chicken and human B cell lines. Proceedings of the National Academy of Sciences of the United States of America 34 30487218
2016 Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4. The Journal of experimental medicine 33 27162139
2011 PIASy inhibits virus-induced and interferon-stimulated transcription through distinct mechanisms. The Journal of biological chemistry 32 21199872
2008 PIASy represses CCAAT/enhancer-binding protein delta (C/EBPdelta) transcriptional activity by sequestering C/EBPdelta to the nuclear periphery. The Journal of biological chemistry 30 18477566
2006 PIASy-mediated repression of the Ets-1 is independent of its sumoylation. Biochemical and biophysical research communications 29 16729975
2011 Caveolin-3 undergoes SUMOylation by the SUMO E3 ligase PIASy: sumoylation affects G-protein-coupled receptor desensitization. The Journal of biological chemistry 27 21362625
2016 Transcriptional repression of SIRT1 by protein inhibitor of activated STAT 4 (PIAS4) in hepatic stellate cells contributes to liver fibrosis. Scientific reports 24 27323886
2004 Convergence of interferon-gamma and progesterone signaling pathways in human endometrium: role of PIASy (protein inhibitor of activated signal transducer and activator of transcription-y). Molecular endocrinology (Baltimore, Md.) 23 15155784
2008 Spatial interplay between PIASy and FIP200 in the regulation of signal transduction and transcriptional activity. Molecular and cellular biology 22 18285457
2018 Alcohol-induced autophagy via upregulation of PIASy promotes HCV replication in human hepatoma cells. Cell death & disease 20 30185779
2010 Rod/Zw10 complex is required for PIASy-dependent centromeric SUMOylation. The Journal of biological chemistry 20 20696768
2007 PIASy controls ubiquitination-dependent proteasomal degradation of Ets-1. The Biochemical journal 19 17456046
2017 SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial Cells. Mediators of inflammation 17 29038616
2017 Dynamics of RIF1 SUMOylation is regulated by PIAS4 in the maintenance of Genomic Stability. Scientific reports 17 29234018
2024 WRN inhibition leads to its chromatin-associated degradation via the PIAS4-RNF4-p97/VCP axis. Nature communications 16 39025847
2016 A post-translational modification cascade employing HDAC9-PIASy-RNF4 axis regulates chondrocyte hypertrophy by modulating Nkx3.2 protein stability. Cellular signalling 16 27312341
2017 Identification of a new small ubiquitin-like modifier (SUMO)-interacting motif in the E3 ligase PIASy. The Journal of biological chemistry 15 28455449
2019 Perturbation of maternal PIASy abundance disrupts zygotic genome activation and embryonic development via SUMOylation pathway. Biology open 14 31640975
2009 PIASy inhibits LRH-1-dependent CYP11A1 expression by competing for SRC-1 binding. The Biochemical journal 14 19067654
2017 Immunosuppression with tacrolimus improved implantation and rescued expression of uterine progesterone receptor and its co-regulators FKBP52 and PIASy at nidation in the obese and diabetic mice: Comparative studies with metformin. Molecular and cellular endocrinology 13 28689771
2010 PIASy interacts with p73alpha and regulates cell cycle in HEK293 cells. Cellular immunology 13 20471636
2022 Cardiac-targeted PIASy gene silencing mediates deSUMOylation of caveolin-3 and prevents ischemia/reperfusion-induced Nav1.5 downregulation and ventricular arrhythmias. Military Medical Research 12 36229865
2020 PIAS4, upregulated in hepatocellular carcinoma, promotes tumorigenicity and metastasis. Journal of cellular biochemistry 12 31943317
2004 The RING domain of PIASy is involved in the suppression of bone morphogenetic protein-signaling pathway. Biochemical and biophysical research communications 12 15158472
2023 Downregulation of cardiac PIASy inhibits Cx43 SUMOylation and ameliorates ventricular arrhythmias in a rat model of myocardial ischemia/reperfusion injury. Chinese medical journal 11 37014755
2012 PIAS4 represses vitamin D receptor-mediated signaling and acts as an E3-SUMO ligase towards vitamin D receptor. The Journal of steroid biochemistry and molecular biology 11 22564762
2018 Chromatin remodeling: demethylating H3K4me3 of type I IFNs gene by Rbp2 through interacting with Piasy for transcriptional attenuation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 28970247
2011 SYT-SSX1 (synovial sarcoma translocated) regulates PIASy ligase activity to cause overexpression of NCOA3 protein. The Journal of biological chemistry 10 21454665
2020 Homeoprotein Msx1-PIASy Interaction Inhibits Angiogenesis. Cells 9 32784646
2019 PIASy is a SUMOylation-independent negative regulator of the insulin transactivator MafA. Journal of molecular endocrinology 9 31614335
2013 Protein inhibitors of activated STAT (Pias1 and Piasy) differentially regulate pituitary homeobox 2 (PITX2) transcriptional activity. The Journal of biological chemistry 9 23515314
2004 Negative regulation of Smad2 by PIASy is required for proper Xenopus mesoderm formation. Development (Cambridge, England) 9 15496439
2016 Protein inhibitor of activated STAT 4 (PIAS4) regulates liver fibrosis through modulating SMAD3 activity. Journal of biomedical research 8 27924068
2016 Protein inhibitor of activated STAT 4 (PIAS4) regulates pro-inflammatory transcription in hepatocytes by repressing SIRT1. Oncotarget 7 27285989
2016 Protein Inhibitor of Activated STAT Y (PIASy) Regulates Insulin Secretion by Interacting with LIM Homeodomain Transcription Factor Isl1. Scientific reports 7 28000708
2013 Impaired PIASy-Tip60 signaling weakens activation of p53 in melanoma. Melanoma research 7 23624367
2012 Protein inhibitor of activated STAT, PIASy regulates α-smooth muscle actin expression by interacting with E12 in mesangial cells. PloS one 7 22829926
2021 Roles of the SUMO-related enzymes, PIAS1, PIAS4, and RNF4, in DNA double-strand break repair by homologous recombination. Biochemical and biophysical research communications 5 35007836
2018 PIASy antagonizes Ras-driven NSCLC survival by promoting GATA2 SUMOylation. Journal of Cancer 4 29760808
2017 Reversible regulation of ORC2 SUMOylation by PIAS4 and SENP2. Oncotarget 4 29050267
2014 SUMO Proteins are not Involved in TGF-β1-induced, Smad3/4-mediated Germline α Transcription, but PIASy Suppresses it in CH12F3-2A B Cells. Immune network 4 25550698
2025 PIASy deficiency mitigates thoracic aortic aneurysm formation via the TGF-β/Smad2/3 pathway. Journal of thoracic disease 2 40529770
2025 Total Flavonoids of Hedyotis Diffusa Willd Suppresses Prostate Cancer Progression by Promoting AR Ubiquitination and Degradation via the PIAS4/STAT3 Pathway. Cell biology international 2 40862474
2024 PIAS4 regulates pluripotency exit and cell fate commitment in porcine embryonic stem cells. Fundamental research 2 40777776
2025 PIAS1/PIAS4-Mediated SUMOylation of TDP-43 Is Induced by Oxidative Stress. bioRxiv : the preprint server for biology 1 41292941
2026 SUMOylation machinery protein, PIAS4 role in breast cancer cell proliferation and drug sensitivity. Molecular biology reports 0 41615552
2026 SIRT5 Inhibits HMGCS2 Succinylation and Promotes Its PIAS4-Dependent Ubiquitination to Attenuate Diabetic Cardiomyopathy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 41626766
2026 PIAS4 inhibition induces cell cycle arrest and exhibits a synergistic effect in combination with CDK4/6 inhibitor in breast cancer treatment. Oncogene 0 41946996
2025 PIASy of orange-spotted grouper (Epinephelus coioides) negatively regulates RLRs-mediated innate antiviral immunity. Fish & shellfish immunology 0 39842679

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