| Structural highlights
Function
SIR2_HUMAN NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and non-histone proteins. Deacetylates 'Lys-40' of alpha-tubulin. Involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton. Deacetylates PCK1, opposing proteasomal degradation. Deacetylates 'Lys-310' of RELA.[1] [2] [3] [4]
Publication Abstract from PubMed
Post-translational modifications (PTMs) regulate numerous proteins and are important for many biological processes. Lysine 4-oxononanoylation (4-ONylation) is a newly discovered histone PTM that prevents nucleosome assembly under oxidative stress. Whether there are cellular enzymes that remove 4-ONyl from histones remains unknown, which hampers the further investigation of the cellular function of this PTM. Here, we report that mammalian SIRT2 can remove 4-ONyl from histones and other proteins in live cells. A crystal structure of SIRT2 in complex with a 4-ONyl peptide reveals a lone pair-pi interaction between Phe119 and the ketone oxygen of the 4-ONyl group. This is the first time that a mechanism to reverse 4-ONyl lysine modification is reported and will help to understand the role of SIRT2 in oxidative stress responses and the function of 4-ONylation.
SIRT2 Reverses 4-Oxononanoyl Lysine Modification on Histones.,Jin J, He B, Zhang X, Lin H, Wang Y J Am Chem Soc. 2016 Sep 28;138(38):12304-7. doi: 10.1021/jacs.6b04977. Epub 2016 , Sep 15. PMID:27610633[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ North BJ, Marshall BL, Borra MT, Denu JM, Verdin E. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003 Feb;11(2):437-44. PMID:12620231
- ↑ Dryden SC, Nahhas FA, Nowak JE, Goustin AS, Tainsky MA. Role for human SIRT2 NAD-dependent deacetylase activity in control of mitotic exit in the cell cycle. Mol Cell Biol. 2003 May;23(9):3173-85. PMID:12697818
- ↑ Rothgiesser KM, Erener S, Waibel S, Luscher B, Hottiger MO. SIRT2 regulates NF-kappaB dependent gene expression through deacetylation of p65 Lys310. J Cell Sci. 2010 Dec 15;123(Pt 24):4251-8. doi: 10.1242/jcs.073783. Epub 2010 Nov, 16. PMID:21081649 doi:10.1242/jcs.073783
- ↑ Jiang W, Wang S, Xiao M, Lin Y, Zhou L, Lei Q, Xiong Y, Guan KL, Zhao S. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol Cell. 2011 Jul 8;43(1):33-44. doi: 10.1016/j.molcel.2011.04.028. PMID:21726808 doi:10.1016/j.molcel.2011.04.028
- ↑ Jin J, He B, Zhang X, Lin H, Wang Y. SIRT2 Reverses 4-Oxononanoyl Lysine Modification on Histones. J Am Chem Soc. 2016 Sep 28;138(38):12304-7. doi: 10.1021/jacs.6b04977. Epub 2016 , Sep 15. PMID:27610633 doi:http://dx.doi.org/10.1021/jacs.6b04977
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