PIAS3
E3 SUMO-protein-ligaza PIAS3 jest enzim koji je kod ljudi kodiran genom PIAS3 sa hromosoma 1.[5][6]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 628 aminokiselina, a molekulska težina 68.017 Da.[7]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MAELGELKHM | VMSFRVSELQ | VLLGFAGRNK | SGRKHELLAK | ALHLLKSSCA | ||||
| PSVQMKIKEL | YRRRFPRKTL | GPSDLSLLSL | PPGTSPVGSP | GPLAPIPPTL | ||||
| LAPGTLLGPK | REVDMHPPLP | QPVHPDVTMK | PLPFYEVYGE | LIRPTTLAST | ||||
| SSQRFEEAHF | TFALTPQQVQ | QILTSREVLP | GAKCDYTIQV | QLRFCLCETS | ||||
| CPQEDYFPPN | LFVKVNGKLC | PLPGYLPPTK | NGAEPKRPSR | PINITPLARL | ||||
| SATVPNTIVV | NWSSEFGRNY | SLSVYLVRQL | TAGTLLQKLR | AKGIRNPDHS | ||||
| RALIKEKLTA | DPDSEVATTS | LRVSLMCPLG | KMRLTVPCRA | LTCAHLQSFD | ||||
| AALYLQMNEK | KPTWTCPVCD | KKAPYESLII | DGLFMEILSS | CSDCDEIQFM | ||||
| EDGSWCPMKP | KKEASEVCPP | PGYGLDGLQY | SPVQGGDPSE | NKKKVEVIDL | ||||
| TIESSSDEED | LPPTKKHCSV | TSAAIPALPG | SKGVLTSGHQ | PSSVLRSPAM | ||||
| GTLGGDFLSS | LPLHEYPPAF | PLGADIQGLD | LFSFLQTESQ | HYGPSVITSL | ||||
| DEQDALGHFF | QYRGTPSHFL | GPLAPTLGSS | HCSATPAPPP | GRVSSIVAPG | ||||
| GALREGHGGP | LPSGPSLTGC | RSDIISLD |
Funkcija
[uredi | uredi izvor]PIAS3 protein također funkcionira kao SUMO (mali modifikator sličan ubikvitinu)-E3 ligaza, koja katalizira kovalentno vezivanje SUMO proteina na specifične ciljne supstrate. Direktno se vezuje za nekoliko faktora transkripcije i ili blokira ili pojačava njihovu aktivnost. Identificirane su alternativno prerađene varijante transkripta ovog gena su ali priroda nekih od ovih varijanti u punoj dužini nije utvrđena.[6]
Porodica PIAS
[uredi | uredi izvor]Sisarska porodica PIAS ima četiri člana: PIAS1, PIAS2, PIAS3 i PIAS4. U rodu Drosophila identificiran je jedan homolog PIAS-a pod nazivom dPIAS/Zimp.[8] In yeast, two PIAS-related proteins were identified namely SIZ1 and SIZ2.[9] Porodica PIAS sadrži više od 60 proteina, od kojih su većina transkripcijski faktori koji se mogu pozitivno ili negativno regulirati putem više mehanizama.
Domeni
[uredi | uredi izvor]SAF-A/B, Acinus i PIAS (SAP) domen nalaze se na N-terminalu PIAS proteina.[10] Ovaj evolucijski konzervirani domen nalazi se u proteinima u rasponu od kvasca do ljudi i dijele ga drugi proteini koji vežu hromatin, kao što su faktor vezivanja skela A i B.[11] Domen SAP prepotznaje i veže AT-bogate sekvence DNK DNA i rigijama dodataka skele i matriksa.[12] Ovi elementi se često nalaze u blizini pojačivača gena i stupaju u interakciju s proteinima jearnog matriksa, kako bi osigurali jedinstveno jedarno mikrookruženje za regulaciju transkripcije. LXXLL potpisni motiv prisutan je u SAP domenu svih PIAS proteina. Pokazalo se da ovaj prepoznatljivi motiv posreduje u interakcijama između jedarnih receptora i njihovih koregulatora.[13] Također je neophodan za vezivanje PIAS3 za androgeni receptor. Motiv LXXLL predstavlja minimalni zahtjev za interakciju sa NFκB p65 podjedinicom i za inhibiciju transkripcijske aktivnosti NFκB. Motiv LXXLL također je odgovoran za zadržavanje PIAS3 u jedru.
Pro-Ile-Asn-Ile-Thr (PINIT) motiv predstavlja visoko konzerviranu regiju PIAS proteina, za koju se pokazalo da je uključena u jedarno zadržavanje PIAS3.[14] Unutar PINIT domena, regija PIAS382-132 izolirana je i okarakterizirana kao inhibitorni domen koji veže i inhibira i transktipcijske faktore MITF i STAT3.[15] RING-prstoliku cink-vezujući domen je jedan od najkonzerviranijih domena porodice PIAS i pokazalo se da je važan za aktivnost PIAS3 kao SUMO-E3 ligaza.[16] The RLD domain is also involved in the positive regulation of SMAD3 by PIAS3.[17]
Interakcije
[uredi | uredi izvor]Pokazalo se da PIAS3 ima interakcije sa:
Srodni genski problemi
[uredi | uredi izvor]Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000131788 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028101 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Ueki N, Seki N, Yano K, Saito T, Masuho Y, Muramatsu M (juni 1999). "Isolation and chromosomal assignment of a human gene encoding protein inhibitor of activated STAT3 (PIAS3)". Journal of Human Genetics. 44 (3): 193–6. doi:10.1007/s100380050141. PMID 10319586. S2CID 12454718.
- ^ a b "Entrez Gene: PIAS3 protein inhibitor of activated STAT, 3".
- ^ "UniProt, Q9Y6X2" (jezik: engleski). Pristupljeno 16. 12. 2021.
- ^ Mohr SE, Boswell RE (Mar 1999). "Zimp encodes a homologue of mouse Miz1 and PIAS3 and is an essential gene in Drosophila melanogaster". Gene. 229 (1–2): 109–16. doi:10.1016/s0378-1119(99)00033-5. PMID 10095110.
- ^ Islam HK, Fujioka Y, Tomidokoro T, Sugiura H, Takahashi T, Kondo S, Katoh H (2001). "Immunohistochemical study of genetic alterations in intraductal and invasive ductal tumors of the pancreas". Hepato-Gastroenterology. 48 (39): 879–83. PMID 11462947.
- ^ Shuai K (Feb 2006). "Regulation of cytokine signaling pathways by PIAS proteins". Cell Research. 16 (2): 196–202. doi:10.1038/sj.cr.7310027. PMID 16474434. S2CID 755228.
- ^ Aravind L, Koonin EV (2000). "SAP - a putative DNA-binding motif involved in chromosomal organization". Trends in Biochemical Sciences. 25 (3): 112–4. doi:10.1016/s0968-0004(99)01537-6. PMID 10694879.
- ^ Kipp, M.; et al. (2000). "SAF-Box, a conserved protein domain that specifically recognizes scaffold attachment region DNA". Mol Cell Biol. 20 (20): 7480–7489. doi:10.1128/mcb.20.20.7480-7489.2000. PMC 86301. PMID 11003645.
- ^ Glass CK, Rosenfeld MG (Jan 2000). "The coregulator exchange in transcriptional functions of nuclear receptors". Genes & Development. 14 (2): 121–41. doi:10.1101/gad.14.2.121 (neaktivno 31. 10. 2021). PMID 10652267.CS1 održavanje: DOI nije aktivan od 2021 (link)
- ^ Duval D, Duval G, Kedinger C, Poch O, Boeuf H (Nov 2003). "The 'PINIT' motif, of a newly identified conserved domain of the PIAS protein family, is essential for nuclear retention of PIAS3L". FEBS Letters. 554 (1–2): 111–8. doi:10.1016/s0014-5793(03)01116-5. PMID 14596924. S2CID 23261716.
- ^ Levy C, Khaled M, Fisher DE (Sep 2006). "MITF: master regulator of melanocyte development and melanoma oncogene". Trends in Molecular Medicine. 12 (9): 406–14. doi:10.1016/j.molmed.2006.07.008. PMID 16899407.
- ^ Nakagawa, K.; Yokosawa, H. (2002). "PIAS3 induces SUMO-1 modification and transcriptional repression of IRF-1". FEBS Lett. 530 (1–3): 204–208. doi:10.1016/s0014-5793(02)03486-5. PMID 12387893. S2CID 38456991.
- ^ Long J, Wang G, Matsuura I, He D, Liu F (Jan 2004). "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. 101 (1): 99–104. Bibcode:2004PNAS..101...99L. doi:10.1073/pnas.0307598100. PMC 314145. PMID 14691252.
- ^ Rödel B, Tavassoli K, Karsunky H, Schmidt T, Bachmann M, Schaper F, Heinrich P, Shuai K, Elsässer HP, Möröy T (Nov 2000). "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3". EMBO J. 19 (21): 5845–55. doi:10.1093/emboj/19.21.5845. PMC 305799. PMID 11060035.
- ^ Zentner MD, Lin HH, Deng HT, Kim KJ, Shih HM, Ann DK (Aug 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". J. Biol. Chem. 276 (32): 29805–14. doi:10.1074/jbc.M103153200. PMID 11390395. S2CID 33084417.
- ^ Yagil Z, Nechushtan H, Kay G, Yang CM, Kemeny DM, Razin E (maj 2010). "The enigma of the role of protein inhibitor of activated STAT3 (PIAS3) in the immune response". Trends Immunol. 31 (5): 199–204. doi:10.1016/j.it.2010.01.005. PMID 20181527.
- ^ a b Long J, Wang G, Matsuura I, He D, Liu F (Jan 2004). "Activation of Smad transcriptional activity by protein inhibitor of activated STAT3 (PIAS3)". Proc. Natl. Acad. Sci. U.S.A. 101 (1): 99–104. Bibcode:2004PNAS..101...99L. doi:10.1073/pnas.0307598100. PMC 314145. PMID 14691252.
- ^ Klopocki E, Schulze H, Strauss G, Ott CE, Hall J, Trotier F, Fleischhauer S, Greenhalgh L, Newbury-Ecob RA, Neumann LM, Habenicht R, König R, Seemanova E, Megarbane A, Ropers HH, Ullmann R, Horn D, Mundlos S (Feb 2007). "Complex inheritance pattern resembling autosomal recessive inheritance involving a microdeletion in thrombocytopenia-absent radius syndrome". American Journal of Human Genetics. 80 (2): 232–40. doi:10.1086/510919. PMC 1785342. PMID 17236129.
Dopunska literatura
[uredi | uredi izvor]- Chung CD, Liao J, Liu B, Rao X, Jay P, Berta P, Shuai K (Dec 1997). "Specific inhibition of Stat3 signal transduction by PIAS3". Science. 278 (5344): 1803–5. Bibcode:1997Sci...278.1803C. doi:10.1126/science.278.5344.1803. PMID 9388184.
- Rödel B, Tavassoli K, Karsunky H, Schmidt T, Bachmann M, Schaper F, Heinrich P, Shuai K, Elsässer HP, Möröy T (Nov 2000). "The zinc finger protein Gfi-1 can enhance STAT3 signaling by interacting with the STAT3 inhibitor PIAS3". The EMBO Journal. 19 (21): 5845–55. doi:10.1093/emboj/19.21.5845. PMC 305799. PMID 11060035.
- Junicho A, Matsuda T, Yamamoto T, Kishi H, Korkmaz K, Saatcioglu F, Fuse H, Muraguchi A (Nov 2000). "Protein inhibitor of activated STAT3 regulates androgen receptor signaling in prostate carcinoma cells". Biochemical and Biophysical Research Communications. 278 (1): 9–13. doi:10.1006/bbrc.2000.3753. PMID 11071847.
- Kotaja N, Aittomäki S, Silvennoinen O, Palvimo JJ, Jänne OA (Dec 2000). "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". Molecular Endocrinology. 14 (12): 1986–2000. doi:10.1210/mend.14.12.0569. PMID 11117529.
- Zentner MD, Lin HH, Deng HT, Kim KJ, Shih HM, Ann DK (Aug 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. 276 (32): 29805–14. doi:10.1074/jbc.M103153200. PMID 11390395. S2CID 33084417.
- Wang LH, Yang XY, Mihalic K, Xiao W, Li D, Farrar WL (Aug 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. 276 (34): 31839–44. doi:10.1074/jbc.M105185200. PMID 11429412. S2CID 24912586.
- Jiménez-Lara AM, Heine MJ, Gronemeyer H (Aug 2002). "PIAS3 (protein inhibitor of activated STAT-3) modulates the transcriptional activation mediated by the nuclear receptor coactivator TIF2". FEBS Letters. 526 (1–3): 142–6. doi:10.1016/S0014-5793(02)03154-X. PMID 12208521. S2CID 2934712.
- Nakagawa K, Yokosawa H (Oct 2002). "PIAS3 induces SUMO-1 modification and transcriptional repression of IRF-1". FEBS Letters. 530 (1–3): 204–8. doi:10.1016/S0014-5793(02)03486-5. PMID 12387893. S2CID 38456991.
- Yamamoto T, Sato N, Sekine Y, Yumioka T, Imoto S, Junicho A, Fuse H, Matsuda T (Jun 2003). "Molecular interactions between STAT3 and protein inhibitor of activated STAT3, and androgen receptor". Biochemical and Biophysical Research Communications. 306 (2): 610–5. doi:10.1016/S0006-291X(03)01026-X. hdl:2115/28119. PMID 12804609.
- Di Y, Li J, Zhang Y, He X, Lu H, Xu D, Ling J, Huo K, Wan D, Li YY, Gu J (Jun 2003). "HCC-associated protein HCAP1, a variant of GEMIN4, interacts with zinc-finger proteins". Journal of Biochemistry. 133 (6): 713–8. doi:10.1093/jb/mvg091. PMID 12869526.
- Cheng J, Zhang D, Zhou C, Marasco WA (Jan 2004). "Down-regulation of SHP1 and up-regulation of negative regulators of JAK/STAT signaling in HTLV-1 transformed cell lines and freshly transformed human peripheral blood CD4+ T-cells". Leukemia Research. 28 (1): 71–82. doi:10.1016/S0145-2126(03)00158-9. PMID 14630083.
- Long J, Wang G, Matsuura I, He D, Liu F (Jan 2004). "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. 101 (1): 99–104. Bibcode:2004PNAS..101...99L. doi:10.1073/pnas.0307598100. PMC 314145. PMID 14691252.
- Nojiri S, Joh T, Miura Y, Sakata N, Nomura T, Nakao H, Sobue S, Ohara H, Asai K, Ito M (Jan 2004). "ATBF1 enhances the suppression of STAT3 signaling by interaction with PIAS3". Biochemical and Biophysical Research Communications. 314 (1): 97–103. doi:10.1016/j.bbrc.2003.12.054. PMID 14715251.
- Wang L, Banerjee S (Jun 2004). "Differential PIAS3 expression in human malignancy". Oncology Reports. 11 (6): 1319–24. doi:10.3892/or.11.6.1319. PMID 15138572.
- Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (Jul 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research. 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.