| Structural highlights
Function
[CTBP1_RAT] Involved in controlling the equilibrium between tubular and stacked structures in the Golgi complex. Corepressor targeting diverse transcription regulators such as GLIS2. Has dehydrogenase activity. Functions in brown adipose tissue (BAT) differentiation.[1] [2] [3] [ZN217_HUMAN] Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'.[4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Numerous transcription factors recruit C-terminal binding protein (CtBP) corepressors. We show that the large zinc finger protein ZNF217 contacts CtBP. ZNF217 is encoded by an oncogene frequently amplified in tumors. ZNF217 contains a typical Pro-X-Asp-Leu-Ser (PXDLS) motif that binds in CtBP's PXDLS-binding cleft. However, ZNF217 also contains a second motif, Arg-Arg-Thr (RRT), that binds a separate surface on CtBP. The crystal structure of CtBP bound to an RRTGAPPAL peptide shows that it contacts a surface crevice distinct from the PXDLS binding cleft. Interestingly, both PXDLS and RRT motifs are also found in other zinc finger proteins, such as RIZ. Finally, we show that ZNF217 represses several promoters, including one from a known CtBP target gene, and mutations preventing ZNF217's contact with CtBP reduce repression. These results identify a new CtBP interaction motif and establish ZNF217 as a transcriptional repressor protein that functions, at least in part, by associating with CtBP.
Specific recognition of ZNF217 and other zinc finger proteins at a surface groove of C-terminal binding proteins.,Quinlan KG, Nardini M, Verger A, Francescato P, Yaswen P, Corda D, Bolognesi M, Crossley M Mol Cell Biol. 2006 Nov;26(21):8159-72. Epub 2006 Aug 28. PMID:16940172[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Spano S, Silletta MG, Colanzi A, Alberti S, Fiucci G, Valente C, Fusella A, Salmona M, Mironov A, Luini A, Corda D. Molecular cloning and functional characterization of brefeldin A-ADP-ribosylated substrate. A novel protein involved in the maintenance of the Golgi structure. J Biol Chem. 1999 Jun 18;274(25):17705-10. PMID:10364211
- ↑ Di Girolamo M, Silletta MG, De Matteis MA, Braca A, Colanzi A, Pawlak D, Rasenick MM, Luini A, Corda D. Evidence that the 50-kDa substrate of brefeldin A-dependent ADP-ribosylation binds GTP and is modulated by the G-protein beta gamma subunit complex. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7065-9. PMID:7624370
- ↑ Nardini M, Spano S, Cericola C, Pesce A, Massaro A, Millo E, Luini A, Corda D, Bolognesi M. CtBP/BARS: a dual-function protein involved in transcription co-repression and Golgi membrane fission. EMBO J. 2003 Jun 16;22(12):3122-30. PMID:12805226 doi:http://dx.doi.org/10.1093/emboj/cdg283
- ↑ Huang G, Krig S, Kowbel D, Xu H, Hyun B, Volik S, Feuerstein B, Mills GB, Stokoe D, Yaswen P, Collins C. ZNF217 suppresses cell death associated with chemotherapy and telomere dysfunction. Hum Mol Genet. 2005 Nov 1;14(21):3219-25. Epub 2005 Oct 3. PMID:16203743 doi:10.1093/hmg/ddi352
- ↑ Krig SR, Jin VX, Bieda MC, O'Geen H, Yaswen P, Green R, Farnham PJ. Identification of genes directly regulated by the oncogene ZNF217 using chromatin immunoprecipitation (ChIP)-chip assays. J Biol Chem. 2007 Mar 30;282(13):9703-12. Epub 2007 Jan 26. PMID:17259635 doi:10.1074/jbc.M611752200
- ↑ Thillainadesan G, Isovic M, Loney E, Andrews J, Tini M, Torchia J. Genome analysis identifies the p15ink4b tumor suppressor as a direct target of the ZNF217/CoREST complex. Mol Cell Biol. 2008 Oct;28(19):6066-77. doi: 10.1128/MCB.00246-08. Epub 2008 Jul , 14. PMID:18625718 doi:10.1128/MCB.00246-08
- ↑ Quinlan KG, Nardini M, Verger A, Francescato P, Yaswen P, Corda D, Bolognesi M, Crossley M. Specific recognition of ZNF217 and other zinc finger proteins at a surface groove of C-terminal binding proteins. Mol Cell Biol. 2006 Nov;26(21):8159-72. Epub 2006 Aug 28. PMID:16940172 doi:10.1128/MCB.00680-06
- ↑ Quinlan KG, Nardini M, Verger A, Francescato P, Yaswen P, Corda D, Bolognesi M, Crossley M. Specific recognition of ZNF217 and other zinc finger proteins at a surface groove of C-terminal binding proteins. Mol Cell Biol. 2006 Nov;26(21):8159-72. Epub 2006 Aug 28. PMID:16940172 doi:10.1128/MCB.00680-06
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