Affinage

PIAS3

E3 SUMO-protein ligase PIAS3 · UniProt Q9Y6X2

Length
628 aa
Mass
68.0 kDa
Annotated
2026-06-10
100 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

PIAS3 is a nuclear SUMO E3 ligase and transcriptional co-regulator that controls signal-dependent gene expression by directly binding transcription factors and/or conjugating SUMO to a broad range of substrates (PMID:9388184, PMID:12387893, PMID:17020914). Its founding activity is direct binding to ligand-activated STAT3, which blocks STAT3 DNA binding and transactivation; this interaction depends on STAT3 Tyr705 phosphorylation and on a PINIT-domain interface (residues 85–272, including L97 and R99), with a short C-terminal acidic fragment additionally engaging the STAT3 coiled-coil domain (PMID:9388184, PMID:19903771, PMID:21812053, PMID:20371673). PIAS3 represses an overlapping set of transcription factors—MITF through its leucine-zipper, plus NF-κB/RelA via an N-terminal LXXLL motif, IRF-1, ATF1, Stat5a/b, progesterone receptor B, and EKLF/KLF1—using both SUMOylation-dependent and SUMOylation-independent modes, and a single short helical motif (residues 82–132) suffices to inhibit both MITF and STAT3 (PMID:11709556, PMID:15140884, PMID:12387893, PMID:17565989, PMID:20854925, PMID:17020914, PMID:25713074, PMID:16368885). Beyond repression, PIAS3 activates TGF-β/SMAD transcription by forming a SMAD3–p300 ternary complex through its RING domain and potentiates HIF-1α by stabilizing the protein independently of ligase activity (PMID:14691252, PMID:37689128, PMID:26697750). As a ligase it SUMOylates Nr2e3, RelA, vimentin, ErbB4 ICD, M2-PK, PLC-γ1, Akt1, MLK3, the cardiac channel Kv4.2, and Smurf1/2, thereby governing photoreceptor rod-versus-cone fate, T-cell PLC-γ1 microcluster assembly, hippocampal LTP via Akt1, ischemic neuronal apoptosis via MLK3, and Kv4 channel surface trafficking (PMID:19186166, PMID:22649547, PMID:21317457, PMID:22584572, PMID:19308990, PMID:30873169, PMID:34288124, PMID:38456949, PMID:39223673, PMID:28423498, PMID:38844181). PIAS3 abundance is tightly controlled: it is degraded following Cys459 S-nitrosation/TRIM32 recruitment, by TRIM8 and by Smad6-recruited Smurf1, by RING-domain-dependent degradation under zinc deficiency (acting as a zinc sensor that relieves STAT3 inhibition), and its MITF interaction is blocked by METTL10-mediated K442 methylation (PMID:17987106, PMID:20516148, PMID:29950561, PMID:38750767, PMID:41114928). PIAS3 also functions in genome maintenance, being uniquely required among PIAS proteins for ATR checkpoint kinase activation (PMID:26565033).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1997 High

    Established PIAS3's founding function: a specific endogenous inhibitor of activated STAT3, defining a post-translational brake on cytokine transcriptional signaling.

    Evidence Co-IP, DNA-binding, and reporter assays in ligand-stimulated cells

    PMID:9388184

    Open questions at the time
    • Did not resolve whether inhibition requires SUMO ligase activity
    • Binding interface on PIAS3 not mapped
  2. 2001 High

    Extended PIAS3's repressor repertoire to MITF, showing it blocks DNA binding of a second lineage-determining transcription factor.

    Evidence In vitro pull-down, Co-IP, EMSA, and reporter assays in mast cells/melanocytes

    PMID:11709556

    Open questions at the time
    • Did not establish whether MITF inhibition involves SUMOylation
    • Did not address how PIAS3 chooses between MITF and STAT3
  3. 2002 Medium

    Defined PIAS3 biochemically as a SUMO E3 ligase, linking its transcriptional repression to RING-dependent SUMO conjugation of a substrate (IRF-1).

    Evidence Yeast two-hybrid, SUMO-1/Ubc9 binding, RING-mutant SUMOylation and reporter assays

    PMID:12387893

    Open questions at the time
    • Single lab
    • SUMO acceptor lysines on IRF-1 not mapped
  4. 2003 High

    Revealed PIAS3 is not solely a repressor: through its RING domain it bridges SMAD3 and p300/CBP to activate TGF-β transcription, establishing context-dependent dual function.

    Evidence Endogenous Co-IP, in vitro binding, RING-domain mutagenesis, reporter assays

    PMID:14691252

    Open questions at the time
    • Did not determine whether SMAD3 is itself SUMOylated
    • Structural basis of ternary complex unresolved
  5. 2004 High

    Mapped the molecular logic of PIAS3 target switching and broadened it to NF-κB, showing PIAS3 inhibits RelA via an N-terminal LXXLL motif and that MITF Ser409 phosphorylation hands PIAS3 from MITF to STAT3.

    Evidence Domain mapping, pull-down, Co-IP, RNAi, reporter assays in melanoma/mast cells

    PMID:15140884 PMID:15572665

    Open questions at the time
    • Stoichiometry of competing complexes not quantified
    • Whether RelA inhibition required SUMOylation not yet tested
  6. 2005 Medium

    Localized a single short helical motif (residues 82–132) sufficient to inhibit both MITF and STAT3, defining a shared inhibitory interface.

    Evidence Domain mapping, 3D modeling, helix-disruption mutagenesis, reporter assays

    PMID:16368885

    Open questions at the time
    • No high-resolution structure
    • Single lab
  7. 2006 High

    Demonstrated PIAS3 represses a nuclear receptor (PRB) by site-specific SUMOylation that drives nuclear export, connecting ligase activity to hormone-dependent promoter recruitment.

    Evidence In vitro/in vivo SUMOylation with Lys mutants, ChIP, nuclear export and reporter assays

    PMID:17020914

    Open questions at the time
    • SUMO isoform specificity not resolved
    • Generality across other nuclear receptors not tested
  8. 2007 High

    Identified the first PIAS3 degradation pathway, showing redox sensing through Cys459 S-nitrosation triggers TRIM32-mediated ubiquitination and global hyposumoylation.

    Evidence S-nitrosation assay, Cys459 mutagenesis, Co-IP, ubiquitination and SUMO-conjugation assays

    PMID:17987106

    Open questions at the time
    • Physiological NO sources driving this in vivo not defined
    • Downstream desumoylated targets not enumerated
  9. 2009 High

    Established that the PIAS3-STAT3 complex shuttles nucleo-cytoplasmically in a STAT3 Tyr705-phosphorylation-dependent manner, linking PIAS3 trafficking to receptor activation kinetics.

    Evidence Confocal imaging, Y705F mutagenesis, Co-IP, fractionation, reporter assays in EGF-stimulated lung cancer cells

    PMID:19903771

    Open questions at the time
    • Nuclear import/export machinery for PIAS3 not identified
    • Whether shuttling applies to non-STAT3 partners unknown
  10. 2009 High

    Defined PIAS3's role in photoreceptor cell-fate specification by SUMOylating Nr2e3 to enforce rod identity and repress cone genes.

    Evidence Co-IP with Crx/Nr2e3, ChIP, in vitro SUMOylation, pharmacological SUMO blockade with phenotype

    PMID:19186166

    Open questions at the time
    • SUMO acceptor site on Nr2e3 not mapped in this study
  11. 2010 High

    Extended the retinal program to cone subtype patterning, showing Pias3-dependent SUMOylation tunes M- versus S-opsin via cone-enriched nuclear receptors.

    Evidence Conditional knockout/knockdown, ChIP, Co-IP, in situ hybridization, electroretinography

    PMID:20729845

    Open questions at the time
    • Direct SUMO substrates among Rxrgamma/Roralpha/Trbeta1 not fully resolved
  12. 2012 High

    Closed the NF-κB regulatory loop by showing PIAS3 acts as a DNA-binding-dependent SUMO E3 ligase for RelA, forming a negative feedback brake on inflammatory transcription.

    Evidence In vivo SUMOylation with RelA and ligase-dead mutants, Co-IP, reporter assays in IκBα-null fibroblasts

    PMID:22649547

    Open questions at the time
    • SUMO acceptor lysine on RelA not specified here
    • Kinetics of feedback in primary immune cells untested
  13. 2012 High

    Showed PIAS3 controls ErbB4 ICD nuclear fate by SUMO-driven sequestration into PML bodies, repressing its transcriptional coactivation and gating mammary differentiation.

    Evidence Co-IP, SUMOylation assay, PML-body co-localization, siRNA rescue, differentiation assays

    PMID:22584572

    Open questions at the time
    • ErbB4 ICD SUMO site not mapped
    • Mechanism of PML targeting unresolved
  14. 2015 High

    Identified PIAS3 as the unique PIAS member required for ATR checkpoint kinase activation, placing it in the DNA-damage response independent of ATRIP SUMOylation.

    Evidence Systematic siRNA of all PIAS members, ATR autophosphorylation and substrate assays under UV/HU/CPT

    PMID:26565033

    Open questions at the time
    • Direct SUMO substrate priming ATR not identified
    • Mechanism of basal ATR activity maintenance unresolved
  15. 2015 High

    Demonstrated SUMOylation-independent co-repression of EKLF/KLF1 controlling erythroid differentiation, and a SUMO-independent stabilization of HIF-1α, broadening PIAS3's non-ligase functions.

    Evidence Endogenous Co-IP, ChIP, LXXLL mutagenesis, siRNA differentiation assays; HIF-1α Co-IP and MG132 rescue

    PMID:25713074 PMID:26697750

    Open questions at the time
    • How PIAS3 stabilizes HIF-1α mechanistically unresolved
    • Distinction between ligase-dependent and -independent target classes not systematized
  16. 2018 High

    Defined a second ubiquitin-mediated PIAS3 degradation route through Smad6-recruited Smurf1, mechanistically linking PIAS3 loss to STAT3 hyperactivation and glioma growth.

    Evidence Co-IP with domain mutants, ubiquitination assay, in vivo glioma model, Smad6 MH2 rescue

    PMID:20516148 PMID:28100038 PMID:29950561

    Open questions at the time
    • Hierarchy among TRIM8/TRIM32/Smurf1 degradation routes unclear
    • Tissue-specific dominance of each pathway untested
  17. 2021 High

    Established neuronal SUMO-ligase functions, showing PIAS3 SUMOylates Akt1 to enhance kinase activity and support hippocampal LTP, while its TrkB-driven dendritic redistribution modulates ERK and GABAergic transmission.

    Evidence Site-specific SUMOylation mutants, SAP-domain Co-IP, Tat-peptide competition, LTP electrophysiology and live imaging

    PMID:34288124 PMID:35307349

    Open questions at the time
    • Endogenous SUMO machinery dynamics in dendrites not resolved
    • Opposing RING vs Ser/Thr domain effects on GABA mechanistically unexplained
  18. 2024 High

    Revealed PIAS3 as a zinc sensor whose RING-domain-dependent degradation under zinc deficiency relieves STAT3 inhibition to restore zinc homeostasis, with cardiac ischemia consequences.

    Evidence Zinc-binding-site and RING-deletion mutants, ubiquitination assay, mouse I/R model, STAT3 activation

    PMID:38750767

    Open questions at the time
    • Ubiquitin ligase mediating zinc-deficiency degradation not identified
    • Direct zinc-occupancy measurement on PIAS3 not provided
  19. 2024 High

    Extended PIAS3 SUMO targets to a cardiac ion channel and to the MLK3 stress kinase, controlling Kv4 surface trafficking and ischemic neuronal apoptosis respectively.

    Evidence Site-specific SUMOylation mutants (Kv4.2-K579, MLK3-K401), electrophysiology, surface biotinylation, in vivo ischemia and behavior

    PMID:38456949 PMID:39223673

    Open questions at the time
    • Whether the same PIAS3 pool serves nuclear and membrane substrates unknown
    • Regulation balancing channel-promoting vs apoptosis-promoting SUMOylation untested
  20. 2025 Medium

    Showed METTL10-mediated K442 methylation of PIAS3 disrupts its MITF binding, stabilizing MITF and rewiring purine metabolism, adding a methylation switch to PIAS3 regulation.

    Evidence MS site identification, Co-IP after K442 methylation, SUMOylation/ubiquitination and MITF stability assays

    PMID:41114928

    Open questions at the time
    • Single lab
    • Whether K442 methylation affects non-MITF substrates untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PIAS3 selects between SUMO-ligase-dependent and -independent modes, and what governs partitioning of a single PIAS3 pool among its many nuclear, cytoplasmic, membrane, and synaptic substrates, remains unresolved.
  • No unifying model for ligase-dependent vs -independent target choice
  • No high-resolution structure of full-length PIAS3 with a substrate
  • Substrate-specific recruitment determinants largely unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 8 GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 4 GO:0140096 catalytic activity, acting on a protein 4
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2
Pathway
R-HSA-392499 Metabolism of proteins 6 R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-168256 Immune System 3 R-HSA-73894 DNA Repair 2
Partners
MITFRELASMAD3SMAD6SMURF1STAT3TRIM32TRIM8

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 PIAS3 binds directly to activated STAT3 (but not STAT1), blocks its DNA-binding activity, and inhibits STAT3-mediated gene activation; the interaction occurs only in cells stimulated with ligands that activate STAT3. Co-immunoprecipitation (in vivo), DNA-binding assay, transcriptional reporter assay Science High 9388184
2000 The zinc finger protein Gfi-1 physically interacts with PIAS3 (yeast two-hybrid and co-precipitation from eukaryotic cells), co-localizes with PIAS3 in nuclear dot structures, and overcomes PIAS3-mediated inhibition of STAT3 transcriptional activity, enhancing IL-6-dependent T-cell activation. Yeast two-hybrid, co-immunoprecipitation, co-localization (nuclear dots), luciferase reporter assay, primary T-cell activation assay The EMBO journal High 11060035
2001 PIAS3 directly associates with MITF (microphthalmia transcription factor) via an in vitro pull-down and co-immunoprecipitation from mast cells and melanocytes, blocking MITF DNA-binding activity and inhibiting MITF-mediated transcriptional activation up to 94%. In vitro pull-down, co-immunoprecipitation, gel-shift (EMSA), luciferase reporter assay (co-transfection) The Journal of biological chemistry High 11709556
2001 Estrogen-activated ER induces PIAS3 mRNA expression and increases physical association of PIAS3 with STAT3, blocking STAT3 DNA binding and transactivation in multiple myeloma cells without directly associating with STAT3, identifying PIAS3 as a co-regulator mediating ER-STAT3 cross-talk. Co-immunoprecipitation, EMSA, reporter assay, RT-PCR The Journal of biological chemistry Medium 11429412
2001 HMGI-C (a Ras/ERK-inducible protein) interacts with PIAS3 (identified by yeast two-hybrid and co-immunoprecipitation); the HMGI-C·PIAS3 complex cooperatively represses both glucocorticoid receptor/dexamethasone-stimulated α-ENaC transcription and STAT3-mediated transactivation. Yeast two-hybrid, co-immunoprecipitation, transcriptional reporter assay, Northern blot The Journal of biological chemistry Medium 11390395
2002 PIAS3 was isolated as an IRF-1-binding protein (yeast two-hybrid), also binds SUMO-1 and the E2 enzyme Ubc9, and SUMOylates IRF-1 in a RING-finger domain-dependent manner, thereby repressing IRF-1 transcriptional activity. Yeast two-hybrid, co-expression SUMOylation assay (RING mutant), transcriptional reporter assay FEBS letters Medium 12387893
2002 PIAS3 interacts in vivo and in vitro with the nuclear receptor coactivator TIF2 through a conserved acidic domain of PIAS3; PIAS3 positively or negatively modulates TIF2-mediated ligand-enhanced transcriptional activation depending on the steroid receptor context. Co-immunoprecipitation (in vivo and in vitro), transcriptional reporter assay FEBS letters Medium 12208521
2003 PIAS3 interacts with Smad proteins (most strongly Smad3) at the endogenous level in mammalian cells and in vitro through the C-terminal domain of Smad3; PIAS3 also interacts with p300/CBP via its RING domain, and PIAS3, Smad3 and p300 form a ternary complex that activates TGF-β/Smad transcriptional responses. A RING-domain mutant unable to bind p300/CBP loses this activation. Co-immunoprecipitation (endogenous and exogenous), in vitro binding, mutagenesis (RING domain mutant), transcriptional reporter assay Proceedings of the National Academy of Sciences of the United States of America High 14691252
2003 The Zip (leucine zipper) domain of MITF mediates direct interaction with PIAS3; phosphorylation of MITF at Ser409 significantly reduces the PIAS3–MITF interaction and diminishes PIAS3's inhibitory effect on MITF transcriptional activity. In vitro pull-down, co-immunoprecipitation, site-directed mutagenesis (phospho-site mutants), luciferase reporter assay Molecular and cellular biology Medium 14645519
2004 PIAS3 associates with the p65/RelA subunit of NF-κB (via an LXXLL motif in the N-terminal region of PIAS3) in vitro (pull-down) and in vivo (Co-IP), inhibits NF-κB-dependent transcription induced by TNF-α, IL-1β, RANK, TNFR1, CD30, and TRAFs, and interferes with p65 binding to the CBP coactivator. Knockdown of PIAS3 by RNAi reverses this inhibition. Yeast two-hybrid, in vitro pull-down, co-immunoprecipitation, luciferase reporter assay, RNAi knockdown, N-terminal domain mapping The Journal of biological chemistry High 15140884
2004 ATBF1 interacts with PIAS3 (yeast two-hybrid, co-immunoprecipitation) and synergistically enhances PIAS3-mediated inhibition of IL-6-activated STAT3, though ATBF1 alone has no effect on STAT3 signaling. Yeast two-hybrid, co-immunoprecipitation, luciferase reporter assay Biochemical and biophysical research communications Medium 14715251
2004 PIAS3 functions as a SUMO-E3 ligase (previously established) and was found to regulate protein stability and function by promoting sumoylation of nuclear proteins; overexpression of PIAS3 induces apoptosis in prostate cancer cell lines in vitro and in vivo. Cell viability/apoptosis assay (in vitro and in vivo xenograft), immunohistochemistry Oncology reports Low 15138572
2004 In cytokine-stimulated cells (gp130, c-Kit receptor activation), phosphorylation of MITF at Ser409 triggers dissociation of PIAS3 from MITF and its re-association with STAT3, demonstrating ligand-dependent switching of PIAS3 between the two transcription factors. Co-immunoprecipitation, phosphorylation analysis, reporter assay in melanoma/mast cells and MITF(di/di) mouse-derived mast cells Molecular and cellular biology Medium 15572665
2005 A 50-amino-acid motif (PIAS82-132) containing two α-helices is sufficient for PIAS3 to inhibit both MITF and STAT3; disruption of one helix abolishes PIAS3 inhibitory activity toward both transcription factors, defining a common binding interface. Domain mapping, 3D protein modeling, mutagenesis (helix disruption), reporter assay Blood Medium 16368885
2006 PIAS3 induces SUMOylation of progesterone receptor B (PRB) at Lys-7, Lys-388, and Lys-531; this SUMOylation inhibits PRB DNA-binding, promotes nuclear export, and represses PRB transactivation of progesterone-responsive genes. The interaction between PIAS3 and PRB is enhanced by progesterone, and PIAS3 is recruited to progesterone-responsive promoters in a hormone-dependent manner. Co-immunoprecipitation (in vitro and in vivo), siRNA knockdown, SUMOylation assay with mutagenesis (Lys→Arg), nuclear export assay, chromatin immunoprecipitation (ChIP), reporter assay Nucleic acids research High 17020914
2007 PIAS3 interacts with ATF1 (yeast two-hybrid, co-immunoprecipitation) and blocks ATF1 DNA binding to the antioxidant-responsive element (ARE) of the ferritin H gene, reversing ATF1-mediated repression. PIAS3 knockdown decreases basal and oxidative-stress-induced ferritin H expression. Yeast two-hybrid, co-immunoprecipitation, EMSA, siRNA knockdown, reporter assay The Journal of biological chemistry Medium 17565989
2007 Nitric oxide (NO) causes S-nitrosation of PIAS3 at Cys459, which promotes interaction with the ubiquitin E3 ligase TRIM32, leading to PIAS3 ubiquitination and degradation (global hyposumoylation). Mutation of Cys459 abolishes NO-stimulated PIAS3–TRIM32 interaction. S-nitrosation assay, co-immunoprecipitation, site-directed mutagenesis (Cys459), ubiquitination assay, SUMO conjugation assay PloS one High 17987106
2008 TRIM8 interacts with PIAS3, causes its proteasomal degradation or nuclear exclusion, cancels the negative effect of PIAS3 on STAT3, and thereby enhances Src-dependent tumorigenesis. Co-immunoprecipitation, ectopic expression, proteasome inhibitor assay, focus formation assay Journal of cell science Medium 20516148
2008 PIAS3 overexpression in osteoclast-lineage transgenic mice impairs osteoclast differentiation (osteopetrotic phenotype); mechanistically, PIAS3 suppresses RANKL-induced expression of c-Fos and NFATc1 and inhibits MITF transcriptional activity independently of sumoylation. PIAS3 overexpression in osteoblasts also downregulates IL-6-induced RANKL expression, indirectly reducing osteoclastogenesis. Transgenic mouse model (TRAP-promoter-driven PIAS3), RANKL-induced osteoclastogenesis assay, siRNA knockdown, reporter assay, co-culture system Blood High 18952894
2009 PIAS3 physically interacts with M2-PK (pyruvate kinase M2) and its isoenzyme M1-PK; endogenous SUMO-1–M2-PK conjugates exist in mammalian cells; PIAS3 expression (but not a RING-domain mutant C299S/H301A) is associated with nuclear localization of M2-PK, suggesting PIAS3 SUMOylates M2-PK to promote its nuclear targeting. Co-immunoprecipitation, SUMO conjugation assay, RING domain mutagenesis, subcellular fractionation/co-localization Journal of cellular biochemistry Medium 19308990
2009 In EGF-stimulated lung cancer cells, PIAS3 forms a complex with STAT3 dependent on STAT3 Tyr705 phosphorylation; within 5 minutes of EGF treatment the PIAS3–STAT3 complex translocates to the nucleus, then PIAS3 returns to the cytoplasm by 30 minutes. Mutation of Tyr705 to Phe reduces PIAS3–STAT3 binding, nuclear translocation of PIAS3, and PIAS3-mediated reduction of STAT3 transcription. Confocal microscopy, co-immunoprecipitation, site-directed mutagenesis (Y705F STAT3), luciferase reporter assay, cellular fractionation Molecular cancer research High 19903771
2009 Pias3 (mouse) is selectively expressed in developing photoreceptors, binds the transcription factors Crx and Nr2e3, is targeted to photoreceptor-specific gene promoters, and SUMOylates Nr2e3, converting it into a potent repressor of cone-specific gene expression. Blocking SUMOylation in photoreceptors produces cells with cone morphological and molecular features and absent rod-specific markers. Co-immunoprecipitation (Pias3 with Crx/Nr2e3), ChIP, in vitro SUMOylation assay, pharmacological SUMOylation blockade, immunofluorescence, gene expression analysis Neuron High 19186166
2010 Pias3-dependent SUMOylation in cone photoreceptors activates M-opsin expression and represses S-opsin expression; the transcription factors Trbeta2 and Rxrgamma mediate preferential Pias3 expression in M cones, and Pias3 directly regulates M and S opsin expression by modulating cone-enriched transcription factors Rxrgamma, Roralpha, and Trbeta1. Conditional knockout/knockdown, reporter assay, ChIP, co-immunoprecipitation, in situ hybridization, electroretinography Nature neuroscience High 20729845
2010 PIAS3 overexpression promotes sumoylation of vimentin at residue 354 (vimentin354) in GBM cells; this sumoylation is associated with inhibition of GBM cell migration and changes in cell shape. Co-immunoprecipitation with SUMO1 antibody, mass spectrometry (proteomic identification), migration assay Oncotarget Medium 21317457
2010 PIAS3 overexpression suppresses Akt phosphorylation and renders lung cancer cells sensitive to chemotherapeutic agents; PIAS3 siRNA knockdown accelerates cell proliferation, worsens chemosensitivity, and augments Akt phosphorylation, placing PIAS3 as a regulator of both JAK/STAT and PI3K/Akt signaling. siRNA knockdown, overexpression, Western blot (phospho-Akt), cell growth/viability assay Neoplasia Medium 17032498
2011 PIAS3 interacts with the STAT3 coiled-coil domain via a short fragment of PIAS3's C-terminal acidic region; a recombinant peptide derived from this region (rPP-C8) suppresses STAT3 target gene expression, inhibits migration and proliferation, and induces apoptosis in cancer cells at low concentrations. Domain mapping (deletion analysis), recombinant peptide internalization assay, STAT3 reporter assay, apoptosis/proliferation assays Molecular cancer research Medium 20371673
2011 The PINIT domain of PIAS3 (residues 85–272) is a folded monomeric domain that directly binds STAT3 in a concentration-dependent manner; L97A, R99N, and R99Q mutations abrogate STAT3 binding, identifying these residues as part of the PIAS3–STAT3 binding interface. Recombinant protein purification, surface plasmon resonance (SPR), site-directed mutagenesis, homology modeling Journal of molecular recognition Medium 21812053
2012 PIAS3 functions as a SUMO E3 ligase for the RelA subunit of NF-κB; PIAS3-mediated SUMOylation of endogenous RelA is induced by NF-κB activation (TNFα), forming a negative regulatory feedback loop. RelA mutants resistant to SUMOylation or PIAS3 SUMO-ligase-dead mutants lose this repression. RelA DNA binding is required as a signal for PIAS3-mediated SUMOylation. In vivo SUMOylation assay, site-directed mutagenesis (SUMOylation-site mutant RelA; SUMO-ligase-dead PIAS3), co-immunoprecipitation, reporter assay, IκBα null fibroblasts PloS one High 22649547
2012 PIAS3 interacts with the ErbB4 intracellular domain (ICD), promotes its SUMO modification, and drives nuclear sequestration of ErbB4 ICD into PML nuclear bodies. PIAS3 overexpression represses ErbB4 ICD coactivation of transcription with YAP; PIAS3 knockdown partially rescues ErbB4-ICD-mediated inhibition of mammary cell differentiation. Co-immunoprecipitation, SUMOylation assay, fluorescence co-localization (PML bodies), siRNA knockdown, transcriptional co-activation reporter assay, differentiation assay The Journal of biological chemistry High 22584572
2013 PIAS3 promotes homology-directed repair (HR) and non-homologous end joining (NHEJ) of DNA double-strand breaks; PIAS3 overexpression increases resistance of HeLa cells to ionizing radiation. DSB repair reporter assay (HR and NHEJ), colony survival after ionizing radiation Oncology letters Low 24137461
2014 N-terminal truncation of Stat5a/b, which occurs post-translationally in prostate cancer cells, removes the N-domain required for binding to PIAS3; PIAS3 inhibits full-length Stat5a/b transcriptional activity in breast cancer cells but not in prostate cancer cells that express the truncated form, indicating that proteolytic removal of the N-terminal domain is a mechanism by which Stat5 evades PIAS3-mediated repression. Western blot, EMSA (DNA binding), co-immunoprecipitation, N-terminal domain mutagenesis, reporter assay The international journal of biochemistry & cell biology Medium 20854925
2015 PIAS3 is required for ATR checkpoint activation: it is the only PIAS family member indispensable for ATR autophosphorylation in response to UV or HU, and for maintaining basal ATR kinase activity prior to DNA damage. PIAS3 is dispensable for ATRIP SUMOylation and the ATR-ATRIP interaction, but loss of PIAS3 reduces phosphorylation of ATR substrates. siRNA knockdown of each PIAS family member, ATR autophosphorylation assay, substrate phosphorylation assay (Western blot), ATR-ATRIP co-immunoprecipitation, DNA damage induction (CPT, UV, HU) The Journal of biological chemistry High 26565033
2015 PIAS3 physically interacts with SMAD2/3 (via the SMAD MH2 domain and PIAS3 RING domain) to activate TGF-β signaling, leading to increased TXNIP expression and ferroptotic susceptibility in HCC cells. Knockdown of TXNIP degrades ferroptosis caused by PIAS3 overexpression; forced TXNIP re-expression restores ferroptosis in PIAS3-knockdown cells. Co-immunoprecipitation, RNA-seq, siRNA knockdown/overexpression, ferroptosis functional assays (lipid peroxidation, cell death) Pharmacological research Medium 37689128
2015 PIAS3 interacts with EKLF/KLF1 transcription factor (co-immunoprecipitation with exogenous and endogenous proteins); PIAS3 acts as a transcriptional co-repressor of EKLF for β-globin and α-hemoglobin stabilizing protein genes independently of sumoylation. The LXXLL motif of PIAS3 is required for transrepression but not for the EKLF-PIAS3 interaction. PIAS3 occupies the β-globin promoter in undifferentiated erythroid cells (ChIP). PIAS3 knockdown accelerates erythroid differentiation. Co-immunoprecipitation (exogenous and endogenous), ChIP, siRNA knockdown, mutagenesis (LXXLL motif), reporter assay, differentiation assay The Journal of biological chemistry High 25713074
2015 PIAS3 enhances HIF-1α transcriptional activity by increasing HIF-1α protein stability through a mechanism independent of PIAS3's SUMO E3 ligase activity; PIAS3 physically associates with HIF-1α, and PIAS3 knockdown destabilizes HIF-1α in a proteasome-dependent manner. Co-immunoprecipitation, PIAS3 overexpression/siRNA knockdown, proteasome inhibitor rescue (MG132), RT-PCR, reporter assay Biochemical and biophysical research communications Medium 26697750
2015 Adenovirus E4-ORF3 specifically sequesters PIAS3 (but not PIAS1, PIAS2, or PIAS4) into a multivalent nuclear matrix, requiring E4-ORF3 polymerization; this PIAS3 targeting is conserved across disparate adenovirus subgroups. Immunofluorescence co-localization, co-immunoprecipitation/pull-down, domain mutants of E4-ORF3 (polymerization-deficient), comparative analysis across adenovirus subgroups Journal of virology Medium 26223632
2017 PIAS3 directly sumoylates Smurf2, and sumoylated Smurf2 (with its E3 ubiquitin ligase activity intact) suppresses invasive growth of breast cancer cell-derived organoids. Genetic ablation of PIAS3 removes this non-invasive constraint. SUMOylation assay, E3 ubiquitin ligase activity mutant, 3D organoid invasion assay, siRNA knockdown Oncotarget Medium 28423498
2017 TRIM8 activates STAT3 signaling in glioblastoma stem-like cells by suppressing PIAS3 expression, most likely through E3-mediated ubiquitination and proteasomal degradation of PIAS3. TRIM8 knockdown reduces p-STAT3 and stem cell markers; STAT3 activation in turn upregulates TRIM8, forming a positive feedback loop. siRNA knockdown, overexpression, Western blot (p-STAT3, stem markers), self-renewal assay, differentiation assay, co-immunoprecipitation Molecular oncology Medium 28100038
2018 Nuclear Smad6 interacts directly with PIAS3 through Smad6's MH2 domain and PIAS3's RING domain; Smad6 recruits Smurf1 (via its MH2 domain and PY motif) to ubiquitinate and degrade PIAS3, reducing PIAS3-mediated STAT3 inhibition and promoting glioma growth. A transducible Smad6 MH2 protein restores PIAS3 expression and reduces gliomagenesis. Co-immunoprecipitation, domain-deletion mutagenesis, ubiquitination assay, in vivo glioma model, Smad6 MH2 transducible protein rescue Nature communications High 29950561
2019 Upon TCR stimulation, PIAS3 (together with PIASxβ) acts as a SUMO E3 ligase for PLC-γ1, promoting its sumoylation at K54, which facilitates PLC-γ1 microcluster assembly and association with SLP76 and Gads adaptors, thereby supporting T cell activation. Co-immunoprecipitation, SUMOylation assay (K54R mutant), confocal imaging (microcluster formation), reporter assay, T cell activation assay Frontiers in immunology Medium 30873169
2021 PIAS3 sumoylates Akt1 at K64 and K276 in response to NMDA receptor-mediated neuronal activity; Akt1 SUMOylation at these sites enhances its kinase activity and T308 phosphorylation. The N-terminal SAP domain of PIAS3 directly binds Akt1; disruption of the Akt1–PIAS3 interaction (using Tat-SAP peptide) inhibits LTP expression and late-phase LTP maintenance in hippocampus, and blocks ERK1/2-BDNF/Arc and mTOR-4E-BP1 cascades. In vivo/in vitro SUMOylation assay (K64R/K276R mutants), co-immunoprecipitation (SAP domain), Tat-fused peptide competition, LTP electrophysiology (hippocampal slices), kinase activity assay FASEB journal High 34288124
2021 BDNF signaling via TrkB facilitates nuclear exodus of PIAS3 and its enrichment in neuronal dendrites; dendritic PIAS3 modulates ERK1/2 kinase pathway signaling and inhibits GABAergic neurotransmission. PIAS3 RING and Ser/Thr domains have opposing effects on GABA-mediated inhibition. In ischemia (OGD), BDNF-TrkB signaling impairs gephyrin clustering at GABAergic synapses through SUMOylation. Live imaging (nuclear exodus), immunofluorescence, PIAS3 domain deletion constructs, GABA receptor electrophysiology, gephyrin cluster analysis, OGD model The Journal of biological chemistry Medium 35307349
2024 AMPK activation enhances PIAS3-mediated SUMOylation of Smurf1 at K324, which increases Smurf1 E3 ubiquitin ligase activity, promotes ALK2 proteolysis, and inhibits BMP signaling, thereby suppressing osteogenic differentiation and traumatic heterotopic ossification. AMPK increases the association between PIAS3 and AMPK. Co-immunoprecipitation, SUMOylation assay (K324R Smurf1 mutant), BMP signaling reporter, osteogenic differentiation assay, ALK2 ubiquitination/degradation assay, heterotopic ossification model Biochimica et biophysica acta. Molecular cell research Medium 38844181
2024 PIAS3 (also known as KChAP) is a bona fide SUMO E3 ligase for the cardiac potassium channels Kv4.2 and HCN2 in HEK cells, and for endogenous Kv4.2 and Kv4.3 in cardiomyocytes. PIAS3-mediated SUMOylation at Kv4.2-K579 increases channel surface expression via a Rab11a-dependent recycling mechanism. PKA phosphorylation at Kv4.2-S552 blocks K579 SUMOylation, reducing Kv4 current, thus PKA and PIAS3 act antagonistically to control channel surface expression. In vitro and cell-based SUMOylation assay (K579R mutant), cardiomyocyte overexpression/knockdown, Rab11a dependence assay, PKA phosphorylation (S552A mutant), electrophysiology (current measurement), surface biotinylation Cell communication and signaling High 39223673
2024 PIAS3 sumoylates MLK3 at K401 (SUMO1 conjugation) following brain ischemia/reperfusion; this SUMOylation promotes MLK3 kinase activation and downstream p38/JNK signaling, leading to neuronal apoptosis. The PINIT domain of PIAS3 mediates direct interaction with MLK3. Overexpression of the PINIT domain (as a dominant negative) disrupts MLK3–PIAS3 interaction, inhibits MLK3 SUMOylation, suppresses downstream signaling, and reduces brain lesion and behavioral deficits in rodent ischemic models. Co-immunoprecipitation, SUMOylation assay (K401R mutant), PIAS3 domain competition (PINIT overexpression), p38/JNK phosphorylation assay, in vivo ischemia model, behavioral testing Cellular and molecular life sciences High 38456949
2024 PIAS3 acts as a zinc sensor: zinc deficiency induces ubiquitination and proteasomal degradation of PIAS3 through its RING finger domain (which contains zinc-binding sites); PIAS3 loss relieves STAT3 inhibition, activating ZIP-family zinc transporter gene expression to restore zinc homeostasis. PIAS3 with a zinc-binding site mutation (PIAS3-Mut) or RING domain deletion is resistant to zinc-deficiency-induced degradation. PIAS3-Mut overexpression worsens myocardial I/R injury. Site-directed mutagenesis (zinc-binding site mutant, RING domain deletion), ubiquitination assay, PIAS3 knockdown/overexpression, cardiac zinc measurement, mouse I/R model (infarct size), STAT3 activation assay Free radical biology & medicine High 38750767
2025 METTL10 methylates PIAS3 at lysine 442 (K442), which disrupts the PIAS3–MITF interaction; as a result, PIAS3-mediated SUMOylation and ubiquitination of MITF are reduced, stabilizing MITF and activating purine metabolism in gastric cancer cells. Mass spectrometry (methylation site identification), co-immunoprecipitation (PIAS3–MITF interaction after K442 methylation), SUMOylation/ubiquitination assay, MITF stability assay Advanced science Medium 41114928

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Specific inhibition of Stat3 signal transduction by PIAS3. Science (New York, N.Y.) 782 9388184
2015 Brassinin inhibits STAT3 signaling pathway through modulation of PIAS-3 and SOCS-3 expression and sensitizes human lung cancer xenograft in nude mice to paclitaxel. Oncotarget 134 25788267
2020 Cancer exosome-derived miR-9 and miR-181a promote the development of early-stage MDSCs via interfering with SOCS3 and PIAS3 respectively in breast cancer. Oncogene 131 32398867
2010 Curcumin suppresses constitutive activation of STAT-3 by up-regulating protein inhibitor of activated STAT-3 (PIAS-3) in ovarian and endometrial cancer cells. Journal of cellular biochemistry 121 20235152
2000 The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3. The EMBO journal 114 11060035
2009 Pias3-dependent SUMOylation directs rod photoreceptor development. Neuron 106 19186166
2004 Differential PIAS3 expression in human malignancy. Oncology reports 104 15138572
2002 PIAS3 induces SUMO-1 modification and transcriptional repression of IRF-1. FEBS letters 100 12387893
2015 Ascochlorin, an isoprenoid antibiotic inhibits growth and invasion of hepatocellular carcinoma by targeting STAT3 signaling cascade through the induction of PIAS3. Molecular oncology 93 25624051
2004 PIAS3 suppresses NF-kappaB-mediated transcription by interacting with the p65/RelA subunit. The Journal of biological chemistry 89 15140884
2013 MicroRNA-18a modulates STAT3 activity through negative regulation of PIAS3 during gastric adenocarcinogenesis. British journal of cancer 87 23322197
2003 Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3). Proceedings of the National Academy of Sciences of the United States of America 83 14691252
2001 A new role for the STAT3 inhibitor, PIAS3: a repressor of microphthalmia transcription factor. The Journal of biological chemistry 75 11709556
2010 TRIM8 modulates STAT3 activity through negative regulation of PIAS3. Journal of cell science 74 20516148
2001 Activation of estrogen receptor blocks interleukin-6-inducible cell growth of human multiple myeloma involving molecular cross-talk between estrogen receptor and STAT3 mediated by co-regulator PIAS3. The Journal of biological chemistry 72 11429412
2008 Human parvovirus B19 NS1 protein modulates inflammatory signaling by activation of STAT3/PIAS3 in human endothelial cells. Journal of virology 70 18550668
2021 Therapeutic Potential of Exosomal circRNA Derived from Synovial Mesenchymal Cells via Targeting circEDIL3/miR-485-3p/PIAS3/STAT3/VEGF Functional Module in Rheumatoid Arthritis. International journal of nanomedicine 65 34887661
2009 The SUMO-E3 ligase PIAS3 targets pyruvate kinase M2. Journal of cellular biochemistry 65 19308990
2017 TRIM8 regulates stemness in glioblastoma through PIAS3-STAT3. Molecular oncology 59 28100038
2020 Epstein-Barr virus-encoded miR-BART5-5p upregulates PD-L1 through PIAS3/pSTAT3 modulation, worsening clinical outcomes of PD-L1-positive gastric carcinomas. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 56 32206940
2006 Overexpression of PIAS3 suppresses cell growth and restores the drug sensitivity of human lung cancer cells in association with PI3-K/Akt inactivation. Neoplasia (New York, N.Y.) 56 17032498
2018 Nuclear Smad6 promotes gliomagenesis by negatively regulating PIAS3-mediated STAT3 inhibition. Nature communications 55 29950561
2017 PAI-1/PIAS3/Stat3/miR-34a forms a positive feedback loop to promote EMT-mediated metastasis through Stat3 signaling in Non-small cell lung cancer. Biochemical and biophysical research communications 55 28988111
2012 NF-κB repression by PIAS3 mediated RelA SUMOylation. PloS one 55 22649547
2004 Interplay between MITF, PIAS3, and STAT3 in mast cells and melanocytes. Molecular and cellular biology 55 15572665
2004 ATBF1 enhances the suppression of STAT3 signaling by interaction with PIAS3. Biochemical and biophysical research communications 50 14715251
1999 Zimp encodes a homologue of mouse Miz1 and PIAS3 and is an essential gene in Drosophila melanogaster. Gene 46 10095110
2013 miRNA-21 inhibition enhances RANTES and IP-10 release in MCF-7 via PIAS3 and STAT3 signalling and causes increased lymphocyte migration. Biochemical and biophysical research communications 44 23998932
2010 The enigma of the role of protein inhibitor of activated STAT3 (PIAS3) in the immune response. Trends in immunology 43 20181527
2010 Pias3-dependent SUMOylation controls mammalian cone photoreceptor differentiation. Nature neuroscience 42 20729845
2007 Nitric oxide destabilizes Pias3 and regulates sumoylation. PloS one 40 17987106
2010 Sumoylation of vimentin354 is associated with PIAS3 inhibition of glioma cell migration. Oncotarget 39 21317457
2012 Protein inhibitor of activated STAT3 (PIAS3) protein promotes SUMOylation and nuclear sequestration of the intracellular domain of ErbB4 protein. The Journal of biological chemistry 37 22584572
2014 Low PIAS3 expression in malignant mesothelioma is associated with increased STAT3 activation and poor patient survival. Clinical cancer research : an official journal of the American Association for Cancer Research 36 25124686
2008 PIAS3 negatively regulates RANKL-mediated osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblasts. Blood 35 18952894
2003 Role played by microphthalmia transcription factor phosphorylation and its Zip domain in its transcriptional inhibition by PIAS3. Molecular and cellular biology 35 14645519
2017 MicroRNA-199a-5p promotes tumour growth by dual-targeting PIAS3 and p27 in human osteosarcoma. Scientific reports 34 28120918
2017 The PIAS3-Smurf2 sumoylation pathway suppresses breast cancer organoid invasiveness. Oncotarget 34 28423498
2007 PIAS3 interacts with ATF1 and regulates the human ferritin H gene through an antioxidant-responsive element. The Journal of biological chemistry 34 17565989
2020 ROR2 suppresses metastasis of prostate cancer via regulation of miR-199a-5p-PIAS3-AKT2 signaling axis. Cell death & disease 33 32415173
2017 Microenvironment regulates the expression of miR-21 and tumor suppressor genes PTEN, PIAS3 and PDCD4 through ZAP-70 in chronic lymphocytic leukemia. Scientific reports 33 28947822
2010 The intracellular delivery of a recombinant peptide derived from the acidic domain of PIAS3 inhibits STAT3 transactivation and induces tumor cell death. Molecular cancer research : MCR 33 20371673
2013 Suppressed Th17 levels correlate with elevated PIAS3, SHP2, and SOCS3 expression in CD4 T cells during acute simian immunodeficiency virus infection. Journal of virology 32 23596301
2001 Requirement for high mobility group protein HMGI-C interaction with STAT3 inhibitor PIAS3 in repression of alpha-subunit of epithelial Na+ channel (alpha-ENaC) transcription by Ras activation in salivary epithelial cells. The Journal of biological chemistry 32 11390395
2009 The association and nuclear translocation of the PIAS3-STAT3 complex is ligand and time dependent. Molecular cancer research : MCR 31 19903771
2023 PIAS3 promotes ferroptosis by regulating TXNIP via TGF-β signaling pathway in hepatocellular carcinoma. Pharmacological research 30 37689128
2018 PIAS3-mediated feedback loops promote chronic colitis-associated malignant transformation. Theranostics 30 29896300
2016 Protein Inhibitor of Activated STAT3 (PIAS3) Is Down-Regulated in Eutopic Endometrium of Women with Endometriosis. Biology of reproduction 30 27226311
2014 miR-125b inhibitor may enhance the invasion-prevention activity of temozolomide in glioblastoma stem cells by targeting PIAS3. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 30 23857508
2002 PIAS3 (protein inhibitor of activated STAT-3) modulates the transcriptional activation mediated by the nuclear receptor coactivator TIF2. FEBS letters 30 12208521
2014 Down-regulation of ATBF1 activates STAT3 signaling via PIAS3 in pacing-induced HL-1 atrial myocytes. Biochemical and biophysical research communications 28 24857987
2006 PIAS3 induction of PRB sumoylation represses PRB transactivation by destabilizing its retention in the nucleus. Nucleic acids research 27 17020914
2005 Identifying a common molecular mechanism for inhibition of MITF and STAT3 by PIAS3. Blood 26 16368885
2019 miR-199a-5p promotes proliferation and metastasis and epithelial-mesenchymal transition through targeting PIAS3 in cervical carcinoma. Journal of cellular biochemistry 25 30937952
2016 SHP2, SOCS3 and PIAS3 Expression Patterns in Medulloblastomas: Relevance to STAT3 Activation and Resveratrol-Suppressed STAT3 Signaling. Nutrients 25 28035977
2015 PIAS3, SHP2 and SOCS3 Expression patterns in Cervical Cancers: Relevance with activation and resveratrol-caused inactivation of STAT3 signaling. Gynecologic oncology 25 26432044
2015 The SUMO (Small Ubiquitin-like Modifier) Ligase PIAS3 Primes ATR for Checkpoint Activation. The Journal of biological chemistry 25 26565033
2009 Polymorphisms in the UBC9 and PIAS3 genes of the SUMO-conjugating system and breast cancer risk. Breast cancer research and treatment 24 19760037
2005 Deficient Stat3 DNA-binding is associated with high Pias3 expression and a positive anti-apoptotic balance in human end-stage alcoholic and hepatitis C cirrhosis. Journal of hepatology 24 16098628
2014 A novel microRNA regulates osteoclast differentiation via targeting protein inhibitor of activated STAT3 (PIAS3). Bone 22 25019593
2021 LncRNA FOXD2-AS1 promotes cell proliferation and invasion of fibroblast-like synoviocytes by regulation of miR-331-3p/PIAS3 pathway in rheumatoid arthritis. Autoimmunity 21 34030529
2015 Adenovirus E4-ORF3 Targets PIAS3 and Together with E1B-55K Remodels SUMO Interactions in the Nucleus and at Virus Genome Replication Domains. Journal of virology 21 26223632
2010 N-terminal truncation of Stat5a/b circumvents PIAS3-mediated transcriptional inhibition of Stat5 in prostate cancer cells. The international journal of biochemistry & cell biology 21 20854925
2018 STAT3/PIAS3 Levels Serve as "Early Signature" Genes in the Development of High-Grade Serous Carcinoma from the Fallopian Tube. Cancer research 20 29339537
2020 The role of PIAS3, p-STAT3 and ALR in colorectal cancer: new translational molecular features for an old disease. European review for medical and pharmacological sciences 17 33155205
2010 Upregulation of SOCS-3 and PIAS-3 impairs IL-12-mediated interferon-gamma response in CD56 T cells in HCV-infected heroin users. PloS one 17 20231901
2018 A positive feedback loop between miR-181b and STAT3 that affects Warburg effect in colon cancer via regulating PIAS3 expression. Journal of cellular and molecular medicine 16 30054984
2011 PIAS3 expression in human gastric carcinoma and its adjacent non-tumor tissues. Clinics and research in hepatology and gastroenterology 16 21334998
2014 PIAS3 suppresses acute graft-versus-host disease by modulating effector T and B cell subsets through inhibition of STAT3 activation. Immunology letters 15 24718277
2013 PIAS3 promotes homology-directed repair and distal non-homologous end joining. Oncology letters 14 24137461
2019 T Cell Receptor (TCR)-Induced PLC-γ1 Sumoylation via PIASxβ and PIAS3 SUMO E3 Ligases Regulates the Microcluster Assembly and Physiological Function of PLC-γ1. Frontiers in immunology 13 30873169
2018 Post-transcriptional regulation of PIAS3 expression by miR-18a in malignant mesothelioma. Molecular oncology 13 30259640
2013 PIAS3 may represent a potential biomarker for diagnosis and therapeutic of human colorectal cancer. Medical hypotheses 13 24120699
2021 PIAS3 suppresses damage in an Alzheimer's disease cell model by inducing the STAT3-associated STAT3/Nestin/Nrf2/HO-1 pathway. Molecular medicine (Cambridge, Mass.) 12 34837964
2015 PIAS3, an inhibitor of STAT3, has intensively negative association with the survival of gastric cancer. International journal of clinical and experimental medicine 12 25785044
2019 YB1 protects cardiac myocytes against H2O2‑induced injury via suppression of PIAS3 mRNA and phosphorylation of STAT3. Molecular medicine reports 11 30942400
2014 Expression of STAT5, COX-2 and PIAS3 in correlation with NSCLC histhopathological features. PloS one 11 25137041
2013 PIAS3 activates the intrinsic apoptotic pathway in non-small cell lung cancer cells independent of p53 status. International journal of cancer 11 23959540
2021 Neuronal activity-induced SUMOylation of Akt1 by PIAS3 is required for long-term potentiation of synaptic transmission. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 10 34288124
2015 Transcriptional activity of erythroid Kruppel-like factor (EKLF/KLF1) modulated by PIAS3 (protein inhibitor of activated STAT3). The Journal of biological chemistry 10 25713074
2015 PIAS3 enhances the transcriptional activity of HIF-1α by increasing its protein stability. Biochemical and biophysical research communications 10 26697750
2021 PIAS3/SOCS1-STAT3 axis responses to oxidative stress in hepatocellular cancer cells. American journal of translational research 9 34956461
2023 Protein inhibitor of activated STAT3 (PIAS3) attenuates psoriasis and associated inflammation. The Journal of dermatology 8 37392066
2022 Trophic factor BDNF inhibits GABAergic signaling by facilitating dendritic enrichment of SUMO E3 ligase PIAS3 and altering gephyrin scaffold. The Journal of biological chemistry 7 35307349
2021 Circ_ZFP644 attenuates caerulein-induced inflammatory injury in rat pancreatic acinar cells by modulating miR-106b/Pias3 axis. Experimental and molecular pathology 7 33945806
2017 Pias3 is necessary for dorso-ventral patterning and visual response of retinal cones but is not required for rod photoreceptor differentiation. Biology open 7 28495965
2016 3-Formylchromone inhibits proliferation and induces apoptosis of multiple myeloma cells by abrogating STAT3 signaling through the induction of PIAS3. Immunopharmacology and immunotoxicology 7 27324722
1999 Isolation and chromosomal assignment of a human gene encoding protein inhibitor of activated STAT3 (PIAS3). Journal of human genetics 7 10319586
2024 AMPK induces PIAS3 mediated SUMOylation of E3 ubiquitin ligase Smurf1 impairing osteogenic differentiation and traumatic heterotopic ossification. Biochimica et biophysica acta. Molecular cell research 6 38844181
2024 PIAS3 acts as a zinc sensor under zinc deficiency and plays an important role in myocardial ischemia/reperfusion injury. Free radical biology & medicine 5 38750767
2024 Crosstalk between PKA and PIAS3 regulates cardiac Kv4 channel SUMOylation. Cell communication and signaling : CCS 5 39223673
2023 Bufalin suppresses esophageal squamous cell carcinoma progression by activating the PIAS3/STAT3 signaling pathway. Journal of thoracic disease 5 37197494
2012 Towards a quantitative understanding of the MITF-PIAS3-STAT3 connection. BMC systems biology 5 22316093
2024 Disrupting PIAS3-mediated SUMOylation of MLK3 ameliorates poststroke neuronal damage and deficits in cognitive and sensorimotor behaviors. Cellular and molecular life sciences : CMLS 4 38456949
2023 Upregulation of tumor suppressor PIAS3 by Honokiol promotes tumor cell apoptosis via selective inhibition of STAT3 tyrosine 705 phosphorylation. Journal of natural medicines 4 38082192
2014 p53 N‑terminal binding and stabilisation by PIAS3 inhibits MDM2‑induced p53 ubiquitination and regulates cell growth. Molecular medicine reports 4 24584189
2013 Decreased expression of PIAS1 and PIAS3 in essential thrombocythemia patients. Genetics and molecular research : GMR 3 24301930
2012 [Expression of STAT3 and PIAS3 in renal tissues of MRL/lpr mice]. Nan fang yi ke da xue xue bao = Journal of Southern Medical University 3 22699062
2025 METTL10-Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 2 41114928
2011 The PINIT domain of PIAS3: structure-function analysis of its interaction with STAT3. Journal of molecular recognition : JMR 2 21812053

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