7kpv

Structural highlights

Function

SSN3_YEAST Component of the SRB8-11 complex. The SRB8-11 complex is a regulatory module of the Mediator complex which is itself involved in regulation of basal and activated RNA polymerase II-dependent transcription. The SRB8-11 complex may be involved in the transcriptional repression of a subset of genes regulated by Mediator. It may inhibit the association of the Mediator complex with RNA polymerase II to form the holoenzyme complex. The SRB8-11 complex phosphorylates the C-terminal domain (CTD) of the largest subunit of RNA polymerase II RPB1 at serines 2 and 5. The SSN3/SRB10 and SSN8/SRB11 kinase-cyclin pair may also positively and negatively regulate numerous transcriptional activators in response to changes in nutritional and physiological conditions. Phosphorylates GCN4, promoting its ubiquitin-mediated degradation, and MSN2, promoting its nuclear exclusion. Phosphorylates STE12, thereby promoting its degradation and inhibition of filamentous growth. Phosphorylates GAL4, and this phosphorylation is required for efficient galactose-inducible transcription. Also phosphorylates BDF1 and the TAF2 subunit of the TFIID complex.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17]}

See Also

• Mediator
• RNA polymerase 3D structures

References

1. ↑ Hirst M, Kobor MS, Kuriakose N, Greenblatt J, Sadowski I. GAL4 is regulated by the RNA polymerase II holoenzyme-associated cyclin-dependent protein kinase SRB10/CDK8. Mol Cell. 1999 May;3(5):673-8. PMID:10360183 doi:10.1016/s1097-2765(00)80360-3
2. ↑ Zaman Z, Ansari AZ, Koh SS, Young R, Ptashne M. Interaction of a transcriptional repressor with the RNA polymerase II holoenzyme plays a crucial role in repression. Proc Natl Acad Sci U S A. 2001 Feb 27;98(5):2550-4. PMID:11226276 doi:10.1073/pnas.041611198
3. ↑ Chi Y, Huddleston MJ, Zhang X, Young RA, Annan RS, Carr SA, Deshaies RJ. Negative regulation of Gcn4 and Msn2 transcription factors by Srb10 cyclin-dependent kinase. Genes Dev. 2001 May 1;15(9):1078-92. PMID:11331604 doi:10.1101/gad.867501
4. ↑ Kang JS, Kim SH, Hwang MS, Han SJ, Lee YC, Kim YJ. The structural and functional organization of the yeast mediator complex. J Biol Chem. 2001 Nov 9;276(45):42003-10. Epub 2001 Sep 12. PMID:11555651 doi:http://dx.doi.org/10.1074/jbc.M105961200
5. ↑ Borggrefe T, Davis R, Erdjument-Bromage H, Tempst P, Kornberg RD. A complex of the Srb8, -9, -10, and -11 transcriptional regulatory proteins from yeast. J Biol Chem. 2002 Nov 15;277(46):44202-7. PMID:12200444 doi:10.1074/jbc.M207195200
6. ↑ Nelson C, Goto S, Lund K, Hung W, Sadowski I. Srb10/Cdk8 regulates yeast filamentous growth by phosphorylating the transcription factor Ste12. Nature. 2003 Jan 9;421(6919):187-90. PMID:12520306 doi:10.1038/nature01243
7. ↑ Liu Y, Kung C, Fishburn J, Ansari AZ, Shokat KM, Hahn S. Two cyclin-dependent kinases promote RNA polymerase II transcription and formation of the scaffold complex. Mol Cell Biol. 2004 Feb;24(4):1721-35. PMID:14749387 doi:10.1128/MCB.24.4.1721-1735.2004
8. ↑ Hallberg M, Polozkov GV, Hu GZ, Beve J, Gustafsson CM, Ronne H, Björklund S. Site-specific Srb10-dependent phosphorylation of the yeast Mediator subunit Med2 regulates gene expression from the 2-microm plasmid. Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3370-5. PMID:14988503 doi:10.1073/pnas.0400221101
9. ↑ Green SR, Johnson AD. Promoter-dependent roles for the Srb10 cyclin-dependent kinase and the Hda1 deacetylase in Tup1-mediated repression in Saccharomyces cerevisiae. Mol Biol Cell. 2004 Sep;15(9):4191-202. PMID:15240822 doi:10.1091/mbc.e04-05-0412
10. ↑ Larschan E, Winston F. The Saccharomyces cerevisiae Srb8-Srb11 complex functions with the SAGA complex during Gal4-activated transcription. Mol Cell Biol. 2005 Jan;25(1):114-23. PMID:15601835 doi:10.1128/MCB.25.1.114-123.2005
11. ↑ Ansari AZ, Ogirala A, Ptashne M. Transcriptional activating regions target attached substrates to a cyclin-dependent kinase. Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2346-9. PMID:15687503 doi:10.1073/pnas.0409671102
12. ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
13. ↑ van de Peppel J, Kettelarij N, van Bakel H, Kockelkorn TT, van Leenen D, Holstege FC. Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets. Mol Cell. 2005 Aug 19;19(4):511-22. PMID:16109375 doi:http://dx.doi.org/10.1016/j.molcel.2005.06.033
14. ↑ Andrau JC, van de Pasch L, Lijnzaad P, Bijma T, Koerkamp MG, van de Peppel J, Werner M, Holstege FC. Genome-wide location of the coactivator mediator: Binding without activation and transient Cdk8 interaction on DNA. Mol Cell. 2006 Apr 21;22(2):179-92. PMID:16630888 doi:http://dx.doi.org/S1097-2765(06)00189-4
15. ↑ Liao SM, Zhang J, Jeffery DA, Koleske AJ, Thompson CM, Chao DM, Viljoen M, van Vuuren HJ, Young RA. A kinase-cyclin pair in the RNA polymerase II holoenzyme. Nature. 1995 Mar 9;374(6518):193-6. PMID:7877695 doi:10.1038/374193a0
16. ↑ Hengartner CJ, Myer VE, Liao SM, Wilson CJ, Koh SS, Young RA. Temporal regulation of RNA polymerase II by Srb10 and Kin28 cyclin-dependent kinases. Mol Cell. 1998 Jul;2(1):43-53. PMID:9702190 doi:10.1016/s1097-2765(00)80112-4
17. ↑ Holstege FC, Jennings EG, Wyrick JJ, Lee TI, Hengartner CJ, Green MR, Golub TR, Lander ES, Young RA. Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998 Nov 25;95(5):717-28. PMID:9845373