PIAS1

Protein inhibitor of activated STAT, 1

PDB rendering based on 1v66.

Available structures
PDB	1v66

Identifiers

Symbols

PIAS1; DDXBP1; GBP; GU/RH-II; MGC141878; MGC141879; ZMIZ3

External IDs

OMIM: 603566 MGI: 1913125 HomoloGene: 22953 GeneCards: PIAS1 Gene

Gene Ontology
Molecular function	• DNA binding • transcription coactivator activity • transcription corepressor activity • protein binding • zinc ion binding • SUMO ligase activity • enzyme binding • metal ion binding • androgen receptor binding
Cellular component	• nucleus • nucleoplasm • nuclear speck
Biological process	• JAK-STAT cascade • cytokine-mediated signaling pathway • androgen receptor signaling pathway • positive regulation of protein sumoylation • positive regulation of transcription, DNA-dependent • interferon-gamma-mediated signaling pathway • regulation of interferon-gamma-mediated signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 15:
68.35 – 68.48 Mb

Chr 9:
62.73 – 62.83 Mb

PubMed search

[1]

[2]

E3 SUMO-protein ligase PIAS1 is an enzyme that in humans is encoded by the PIAS1 gene.^[1]^[2]^[3]

This gene encodes a member of the mammalian PIAS [protein inhibitor of activated STAT-1 (signal transducer and activator of transcription-1)] family. This member contains a putative zinc-binding motif and a highly acidic region. It inhibits STAT1-mediated gene activation and the DNA binding activity, binds to Gu protein/RNA helicase II/DEAD box polypeptide 21, and interacts with androgen receptor (AR). It functions in testis as a nuclear receptor transcriptional coregulator and may have a role in AR initiation and maintenance of spermatogenesis.^[3]

Interactions

PIAS1 has been shown to interact with DNMT3A,^[4] STAT1,^[5] Small ubiquitin-related modifier 1,^[6]^[7] Sp3 transcription factor,^[8] UBE2I^[6]^[8]^[7] and P53.^[9]^[7]

References

^ Liu B, Liao J, Rao X, Kushner SA, Chung CD, Chang DD, Shuai K (Sep 1998). "Inhibition of Stat1-mediated gene activation by PIAS1". Proc Natl Acad Sci U S A 95 (18): 10626–10631. doi:10.1073/pnas.95.18.10626. PMC 27945. PMID 9724754. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=27945.
^ Valdez BC, Henning D, Perlaky L, Busch RK, Busch H (Jul 1997). "Cloning and characterization of Gu/RH-II binding protein". Biochem Biophys Res Commun 234 (2): 335–340. doi:10.1006/bbrc.1997.6642. PMID 9177271.
^ ^a ^b "Entrez Gene: PIAS1 protein inhibitor of activated STAT, 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8554.
^ Ling, Yan; Sankpal Umesh T, Robertson Andrea K, McNally James G, Karpova Tatiana, Robertson Keith D (2004). "Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription". Nucleic Acids Res. (England) 32 (2): 598–610. doi:10.1093/nar/gkh195. PMC 373322. PMID 14752048. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=373322.
^ Liao, J; Fu Y, Shuai K (May. 2000). "Distinct roles of the NH2- and COOH-terminal domains of the protein inhibitor of activated signal transducer and activator of transcription (STAT) 1 (PIAS1) in cytokine-induced PIAS1-Stat1 interaction". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 97 (10): 5267–5272. doi:10.1073/pnas.97.10.5267. ISSN 0027-8424. PMC 25817. PMID 10805787. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=25817.
^ ^a ^b Lee, Byoung-Hee; Yoshimatsu Kumiko, Maeda Akihiko, Ochiai Kazuhiko, Morimatsu Masami, Araki Koichi, Ogino Michiko, Morikawa Shigeru, Arikawa Jiro (Dec. 2003). "Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules". Virus Res. (Netherlands) 98 (1): 83–91. doi:10.1016/j.virusres.2003.09.001. ISSN 0168-1702. PMID 14609633.
^ ^a ^b ^c Kahyo, T; Nishida T, Yasuda H (Sep. 2001). "Involvement of PIAS1 in the sumoylation of tumor suppressor p53". Mol. Cell (United States) 8 (3): 713–718. doi:10.1016/S1097-2765(01)00349-5. ISSN 1097-2765. PMID 11583632.
^ ^a ^b Sapetschnig, Alexandra; Rischitor Grigore, Braun Harald, Doll Andreas, Schergaut Marion, Melchior Frauke, Suske Guntram (Oct. 2002). "Transcription factor Sp3 is silenced through SUMO modification by PIAS1". EMBO J. (England) 21 (19): 5206–5215. doi:10.1093/emboj/cdf510. ISSN 0261-4189. PMC 129032. PMID 12356736. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=129032.
^ Gallagher, W M; Argentini M, Sierra V, Bracco L, Debussche L, Conseiller E (Jun. 1999). "MBP1: a novel mutant p53-specific protein partner with oncogenic properties". Oncogene (ENGLAND) 18 (24): 3608–3616. doi:10.1038/sj.onc.1202937. ISSN 0950-9232. PMID 10380882.

Tan J, Hall SH, Hamil KG et al. (2000). "Protein inhibitor of activated STAT-1 (signal transducer and activator of transcription-1) is a nuclear receptor coregulator expressed in human testis". Mol. Endocrinol. 14 (1): 14–26. doi:10.1210/me.14.1.14. PMID 10628744.
Liao J, Fu Y, Shuai K (2000). "Distinct roles of the NH2- and COOH-terminal domains of the protein inhibitor of activated signal transducer and activator of transcription (STAT) 1 (PIAS1) in cytokine-induced PIAS1-Stat1 interaction". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5267–5272. doi:10.1073/pnas.97.10.5267. PMC 25817. PMID 10805787. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=25817.
Kotaja N, Aittomäki S, Silvennoinen O et al. (2001). "ARIP3 (androgen receptor-interacting protein 3) and other PIAS (protein inhibitor of activated STAT) proteins differ in their ability to modulate steroid receptor-dependent transcriptional activation". Mol. Endocrinol. 14 (12): 1986–2000. doi:10.1210/me.14.12.1986. PMID 11117529.
Gross M, Liu B, Tan J et al. (2001). "Distinct effects of PIAS proteins on androgen-mediated gene activation in prostate cancer cells". Oncogene 20 (29): 3880–3887. doi:10.1038/sj.onc.1204489. PMID 11439351.
Liu B, Shuai K (2001). "Induction of apoptosis by protein inhibitor of activated Stat1 through c-Jun NH2-terminal kinase activation". J. Biol. Chem. 276 (39): 36624–36631. doi:10.1074/jbc.M101085200. PMID 11451946.
Kahyo T, Nishida T, Yasuda H (2001). "Involvement of PIAS1 in the sumoylation of tumor suppressor p53". Mol. Cell 8 (3): 713–718. doi:10.1016/S1097-2765(01)00349-5. PMID 11583632.
Weiskirchen R, Moser M, Weiskirchen S et al. (2001). "LIM-domain protein cysteine- and glycine-rich protein 2 (CRP2) is a novel marker of hepatic stellate cells and binding partner of the protein inhibitor of activated STAT1". Biochem. J. 359 (Pt 3): 485–96. doi:10.1042/0264-6021:3590485. PMC 1222169. PMID 11672422. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1222169.
Megidish T, Xu JH, Xu CW (2002). "Activation of p53 by protein inhibitor of activated Stat1 (PIAS1)". J. Biol. Chem. 277 (10): 8255–8259. doi:10.1074/jbc.C200001200. PMID 11788578.
Schmidt D, Müller S (2002). "Members of the PIAS family act as SUMO ligases for c-Jun and p53 and repress p53 activity". Proc. Natl. Acad. Sci. U.S.A. 99 (5): 2872–2877. doi:10.1073/pnas.052559499. PMC 122440. PMID 11867732. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=122440.
Tan JA, Hall SH, Hamil KG et al. (2002). "Protein inhibitors of activated STAT resemble scaffold attachment factors and function as interacting nuclear receptor coregulators". J. Biol. Chem. 277 (19): 16993–17001. doi:10.1074/jbc.M109217200. PMID 11877418.
Nishida T, Yasuda H (2003). "PIAS1 and PIASxalpha function as SUMO-E3 ligases toward androgen receptor and repress androgen receptor-dependent transcription". J. Biol. Chem. 277 (44): 41311–41317. doi:10.1074/jbc.M206741200. PMID 12177000.
Rui HL, Fan E, Zhou HM et al. (2003). "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. 277 (45): 42981–42986. doi:10.1074/jbc.M208099200. PMID 12223491.
Sapetschnig A, Rischitor G, Braun H et al. (2002). "Transcription factor Sp3 is silenced through SUMO modification by PIAS1". EMBO J. 21 (19): 5206–5215. doi:10.1093/emboj/cdf510. PMC 129032. PMID 12356736. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=129032.
Miyauchi Y, Yogosawa S, Honda R et al. (2003). "Sumoylation of Mdm2 by protein inhibitor of activated STAT (PIAS) and RanBP2 enzymes". J. Biol. Chem. 277 (51): 50131–50136. doi:10.1074/jbc.M208319200. PMID 12393906.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Ungureanu D, Vanhatupa S, Kotaja N et al. (2004). "PIAS proteins promote SUMO-1 conjugation to STAT1". Blood 102 (9): 3311–3313. doi:10.1182/blood-2002-12-3816. PMID 12855578.
Kadaré G, Toutant M, Formstecher E et al. (2004). "PIAS1-mediated sumoylation of focal adhesion kinase activates its autophosphorylation". J. Biol. Chem. 278 (48): 47434–47440. doi:10.1074/jbc.M308562200. PMID 14500712.
Tallec LP, Kirsh O, Lecomte MC et al. (2004). "Protein inhibitor of activated signal transducer and activator of transcription 1 interacts with the N-terminal domain of mineralocorticoid receptor and represses its transcriptional activity: implication of small ubiquitin-related modifier 1 modification". Mol. Endocrinol. 17 (12): 2529–2542. doi:10.1210/me.2003-0299. PMID 14500761.

PDB gallery

1v66: Solution structure of human p53 binding domain of PIAS-1

JAK-STAT signaling pathway

Ligand

Cytokine

Cytokine receptor

Type I cytokine receptor · Type II cytokine receptor

Janus kinase

JAK1 · JAK2 · JAK3 · TYK2

Adaptor proteins

STAT	STAT1 · STAT2 · STAT3 · STAT4 · STAT5 · STAT6

PIAS	PIAS1 · PIAS2 · PIAS3 · PIAS4

SOCS	1, 2, 3, 4, 5, 6, 7

IRF	IRF1 · IRF2 · IRF3 · IRF4 · IRF5 · IRF6 · IRF7 · IRF8

B trdu: iter (nrpl/grfl/cytl/horl), csrc (lgic, enzr, gprc, igsr, intg, nrpr/grfr/cytr), itra (adap, gbpr, mapk), calc, lipd; path (hedp, wntp, tgfp+mapp, notp, jakp, fsap, hipp, tlrp)

PIAS1

Interactions

References

Further reading