Gene Symbol: Pias4
Description: protein inhibitor of activated STAT 4
Alias: PIASY, Pias-gamma, Piasg, E3 SUMO-protein ligase PIAS4, RING-type E3 ubiquitin transferase PIAS4, protein inhibitor of activated STAT PIASy, protein inhibitor of activated STAT protein 4, protein inhibitor of activated STAT protein gamma
Species: mouse
Products:     Pias4

Top Publications

  1. Sachdev S, Bruhn L, Sieber H, Pichler A, Melchior F, Grosschedl R. PIASy, a nuclear matrix-associated SUMO E3 ligase, represses LEF1 activity by sequestration into nuclear bodies. Genes Dev. 2001;15:3088-103 pubmed
    ..of additional regulatory mechanisms of LEF1 function, we identified the protein inhibitor of activated STAT, PIASy, as a novel interaction partner of LEF1...
  2. Imoto S, Sugiyama K, Muromoto R, Sato N, Yamamoto T, Matsuda T. Regulation of transforming growth factor-beta signaling by protein inhibitor of activated STAT, PIASy through Smad3. J Biol Chem. 2003;278:34253-8 pubmed
    ..study we identified a protein inhibitor of activated STAT (signal transducers and activators of transcription), PIASy, as a novel interaction partner of Smad7 by yeast two-hybrid screening using the MH2 domain of Smad7 as bait...
  3. Nelson V, Davis G, Maxwell S. A putative protein inhibitor of activated STAT (PIASy) interacts with p53 and inhibits p53-mediated transactivation but not apoptosis. Apoptosis. 2001;6:221-34 pubmed
    ..We report here that the PIASy member of the protein inhibitor of activated STAT family inhibited p53's transactivation function without ..
  4. Chun T, Itoh H, Subramanian L, INIGUEZ LLUHI J, Nakao K. Modification of GATA-2 transcriptional activity in endothelial cells by the SUMO E3 ligase PIASy. Circ Res. 2003;92:1201-8 pubmed
    ..We have identified PIASy in a search for new GATA-2 interacting proteins that can regulate GATA-2-mediated endothelial gene expression...
  5. Collavin L, Gostissa M, Avolio F, Secco P, Ronchi A, Santoro C, et al. Modification of the erythroid transcription factor GATA-1 by SUMO-1. Proc Natl Acad Sci U S A. 2004;101:8870-5 pubmed
    ..We show that the nuclear RING finger protein PIASy promotes sumoylation of GATA-1 and dramatically represses its transcriptional activity...
  6. Albor A, El Hizawi S, Horn E, Laederich M, Frosk P, Wrogemann K, et al. 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. J Biol Chem. 2006;281:25850-66 pubmed
    ..Here we report that Trim32 interacts with Piasy and promotes Piasy ubiquitination and degradation...
  7. Yueh A, Leung J, Bhattacharyya S, Perrone L, De los Santos K, Pu S, et al. Interaction of moloney murine leukemia virus capsid with Ubc9 and PIASy mediates SUMO-1 addition required early in infection. J Virol. 2006;80:342-52 pubmed
    Yeast two-hybrid screens led to the identification of Ubc9 and PIASy, the E2 and E3 small ubiquitin-like modifier (SUMO)-conjugating enzymes, as proteins interacting with the capsid (CA) protein of the Moloney murine leukemia virus...
  8. Costa M, Lee S, Furtado M, Xin L, Sparrow D, Martinez C, et al. Complex SUMO-1 regulation of cardiac transcription factor Nkx2-5. PLoS ONE. 2011;6:e24812 pubmed publisher
    ..We also observe SUMOylation of Nkx2-5 cofactors, which may be critical to Nkx2-5 regulation. Our data reveal highly complex regulatory mechanisms driven by SUMOylation to modulate Nkx2-5 activity. ..
  9. Sun L, Fan Z, Chen J, Tian W, Li M, Xu H, et al. Protein inhibitor of activated STAT 4 (PIAS4) regulates pro-inflammatory transcription in hepatocytes by repressing SIRT1. Oncotarget. 2016;7:42892-42903 pubmed publisher
    ..the regulation of pro-inflammatory transcription in hepatocytes by protein inhibitor of activated STAT 4 (PIAS4) in this process and the underlying mechanisms...

More Information


  1. Roth W, Sustmann C, Kieslinger M, Gilmozzi A, Irmer D, Kremmer E, et al. PIASy-deficient mice display modest defects in IFN and Wnt signaling. J Immunol. 2004;173:6189-99 pubmed
    ..In particular, PIASy has been shown to inhibit the activation of gene expression by the IFN-responsive transcription factor STAT1 and ..
  2. Wang J, Sun Z, Zhang Z, Saadi I, Wang J, Li X, et al. Protein inhibitors of activated STAT (Pias1 and Piasy) differentially regulate pituitary homeobox 2 (PITX2) transcriptional activity. J Biol Chem. 2013;288:12580-95 pubmed publisher
    ..b>Piasy and Pias1 proteins are expressed during craniofacial/tooth development and directly interact and differentially ..
  3. Liu Y, Lagowski J, Gao S, Raymond J, White C, Kulesz Martin M. Regulation of the psoriatic chemokine CCL20 by E3 ligases Trim32 and Piasy in keratinocytes. J Invest Dermatol. 2010;130:1384-90 pubmed publisher
    ..We previously showed that Trim32 binds to the protein inhibitor of activated STAT-Y (Piasy) and mediates its degradation through ubiquitination...
  4. Lee G, Jang H, Lee J, Huh J, Choi S, Chung J, et al. PIASy-mediated sumoylation of SREBP1c regulates hepatic lipid metabolism upon fasting signaling. Mol Cell Biol. 2014;34:926-38 pubmed publisher
    ..demonstrate that the small ubiquitin-related modifier (SUMO) E3 ligase, a protein inhibitor of activated STAT Y (PIASy), sumoylates SREBP1c at Lys98, leading to suppression of the hepatic lipogenic program upon fasting-induced ..
  5. Sun L, Li H, Chen J, Iwasaki Y, Kubota T, Matsuoka M, et al. PIASy mediates hypoxia-induced SIRT1 transcriptional repression and epithelial-to-mesenchymal transition in ovarian cancer cells. J Cell Sci. 2013;126:3939-47 pubmed publisher
    ..Further analysis revealed that the SUMO E3 ligase PIASy (also known as PIAS4) was induced by hypoxia and prevented Sp1 from binding to the SIRT1 promoter...
  6. Sturm S, Koch M, White F. Cloning and analysis of a murine PIAS family member, PIASgamma, in developing skin and neurons. J Mol Neurosci. 2000;14:107-21 pubmed
    ..Thus PIASgamma exhibits a highly selective pattern of expression, suggesting that it modulates the response of cells to developmental cues. ..
  7. Torikoshi K, Abe H, Matsubara T, Hirano T, Ohshima T, Murakami T, et al. Protein inhibitor of activated STAT, PIASy regulates ?-smooth muscle actin expression by interacting with E12 in mesangial cells. PLoS ONE. 2012;7:e41186 pubmed publisher
    ..We found that PIASy, one of the protein inhibitors of activated STAT family protein, interacted with E12 by yeast two-hybrid screens ..
  8. Galleguillos D, Vecchiola A, Fuentealba J, Ojeda V, Alvarez K, Gomez A, et al. PIASgamma represses the transcriptional activation induced by the nuclear receptor Nurr1. J Biol Chem. 2004;279:2005-11 pubmed
    ..In conclusion, our studies identified PIASgamma as a transcriptional co-regulator of Nurr1 and suggest that this interaction may have a physiological role in regulating the expression of Nurr1 target genes. ..
  9. Rui H, Fan E, Zhou H, Xu Z, Zhang Y, Lin S. SUMO-1 modification of the C-terminal KVEKVD of Axin is required for JNK activation but has no effect on Wnt signaling. J Biol Chem. 2002;277:42981-6 pubmed
    ..interacts with three SUMO-1 (small ubiquitin-related modifier) conjugating enzymes 3 (E3), PIAS1, PIASxbeta, and PIASy. The extreme C-terminal six amino acid residues of Axin are critical for the Axin/E3 interaction as deletion of ..
  10. Sturm S, Koch M, White F. Genomic organization of the gene for mouse PIASgamma and analysis of its promoter. Gene. 2001;266:123-30 pubmed
    ..4 kb genomic fragment containing the mouse PIASgamma promoter allowed us to map the transcription 'Start' site of the gene, determine the sequences essential for the activity of this promoter and to define a minimal promoter region. ..
  11. Martin N, Schwamborn K, Schreiber V, Werner A, Guillier C, Zhang X, et al. PARP-1 transcriptional activity is regulated by sumoylation upon heat shock. EMBO J. 2009;28:3534-48 pubmed publisher
    ..Here we show that the SUMO E3 ligase PIASy interacts with the poly(ADP-ribose) polymerase PARP-1, and that PIASy mediates heat shock-induced poly-sumoylation ..
  12. Lear T, McKelvey A, Rajbhandari S, Dunn S, Coon T, Connelly W, et al. Ubiquitin E3 ligase FIEL1 regulates fibrotic lung injury through SUMO-E3 ligase PIAS4. J Exp Med. 2016;213:1029-46 pubmed publisher
    The E3 small ubiquitin-like modifier (SUMO) protein ligase protein inhibitor of activated STAT 4 (PIAS4) is a pivotal protein in regulating the TGFβ pathway...
  13. Martin N, Schwamborn K, Urlaub H, Gan B, Guan J, Dejean A. Spatial interplay between PIASy and FIP200 in the regulation of signal transduction and transcriptional activity. Mol Cell Biol. 2008;28:2771-81 pubmed publisher
    ..We report here the identification of FIP200 (focal adhesion kinase family-interacting protein of 200 kDa) as a new PIASy-interacting protein...
  14. Tolkunova E, Malashicheva A, Parfenov V, Sustmann C, Grosschedl R, Tomilin A. PIAS proteins as repressors of Oct4 function. J Mol Biol. 2007;374:1200-12 pubmed
    ..of Oct4 activity, we performed a yeast two-hybrid screen with the Oct4 POU domain as a bait and isolated PIASy as an Oct4-interacting protein...
  15. Pourcet B, Pineda Torra I, Derudas B, Staels B, Glineur C. SUMOylation of human peroxisome proliferator-activated receptor alpha inhibits its trans-activity through the recruitment of the nuclear corepressor NCoR. J Biol Chem. 2010;285:5983-92 pubmed publisher
    ..The E2-conjugating enzyme Ubc9 and the SUMO E3- ligase PIASy are implicated in this process. In addition, ligand treatment decreases the SUMOylation rate of hPPARalpha...
  16. Kang X, Li J, Zou Y, Yi J, Zhang H, Cao M, et al. PIASy stimulates HIF1? SUMOylation and negatively regulates HIF1? activity in response to hypoxia. Oncogene. 2010;29:5568-78 pubmed publisher
    ..However, how HIF1? became SUMOylated during hypoxia is still unknown. In this study we identify PIASy as a specific E3 ligase for hypoxia-induced HIF1? SUMOylation...
  17. Kuwata T, Nakamura T. BCL11A is a SUMOylated protein and recruits SUMO-conjugation enzymes in its nuclear body. Genes Cells. 2008;13:931-40 pubmed publisher
    ..These results suggest that BCL11A could be involved in the SUMO conjugation system, and that BCL11A might play an important role in protein modification. ..
  18. Stilmann M, Hinz M, Arslan S, Zimmer A, Schreiber V, Scheidereit C. A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation. Mol Cell. 2009;36:365-78 pubmed publisher
    ..The SUMO-1 ligase PIASy and the kinase ataxia talengiectasia mutated (ATM) have been implicated to SUMOylate and phosphorylate nuclear ..
  19. Prigge J, Schmidt E. Interaction of protein inhibitor of activated STAT (PIAS) proteins with the TATA-binding protein, TBP. J Biol Chem. 2006;281:12260-9 pubmed
    ..Mammals issue seven known PIAS proteins from four pias genes, pias1, pias3, piasx, and piasy, each with different cell type-specific expression patterns; the TBP-interacting domain reported here is the only ..
  20. Morita Y, Kanei Ishii C, Nomura T, Ishii S. TRAF7 sequesters c-Myb to the cytoplasm by stimulating its sumoylation. Mol Biol Cell. 2005;16:5433-44 pubmed
    ..The c-myb proto-oncogene product (c-Myb) regulates proliferation and differentiation of hematopoietic cells. PIASy is the only known SUMO E3 ligase for c-Myb...
  21. Tahk S, Liu B, Chernishof V, Wong K, Wu H, Shuai K. Control of specificity and magnitude of NF-kappa B and STAT1-mediated gene activation through PIASy and PIAS1 cooperation. Proc Natl Acad Sci U S A. 2007;104:11643-8 pubmed
    ..Here we report that PIASy, a member of the PIAS (for protein inhibitor of activated STAT) protein family, is a physiologically important ..
  22. Van Dyck F, Delvaux E, Van de Ven W, Chavez M. Repression of the Transactivating Capacity of the Oncoprotein PLAG1 by SUMOylation. J Biol Chem. 2004;279:36121-31 pubmed
    ..Nuclear distribution of PLAG1 was not measurably influenced. Our results suggest a direct repression of the transactivating capacity of the oncoprotein PLAG1 by SUMOylation. ..
  23. Kubota T, Matsuoka M, Xu S, Otsuki N, Takeda M, Kato A, et al. PIASy inhibits virus-induced and interferon-stimulated transcription through distinct mechanisms. J Biol Chem. 2011;286:8165-75 pubmed publisher
    ..Here, we show that PIASy negatively regulates type I interferon (IFN) transcription...
  24. Wong K, Kim R, Christofk H, Gao J, Lawson G, Wu H. 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. Mol Cell Biol. 2004;24:5577-86 pubmed
    Protein inhibitor of activated STAT Y (PIASy) is the shortest member of the PIAS family and has been reported to modulate the transcriptional activities of STAT1, lymphoid enhancer factor 1 (LEF-1), and the androgen receptor...
  25. Bischof O, Schwamborn K, Martin N, Werner A, Sustmann C, Grosschedl R, et al. The E3 SUMO ligase PIASy is a regulator of cellular senescence and apoptosis. Mol Cell. 2006;22:783-94 pubmed
    ..Here we show that overexpression of the E3 SUMO ligase PIASy in normal human fibroblasts recruits the p53 and Rb tumor suppressor pathways to provoke a senescence arrest...