Abstract
The human SIRT5 gene was first identified in 1999 using the sequence of yeast SIR2 protein (Frye RA, BiophysRes Commun 260:273–279, 1999). Sequence analysis suggests that it is more similar to prokaryotic sirtuins (Frye RA, BiophysRes Commun 260:273–279, 1999, Res Commun 273:793–798, 2000). Among the seven mammalian sirtuins, SIRT5 played a special role in our understanding of sirtuin enzymatic activity as it was the first sirtuin that was found to have a novel enzymatic activity other than the well-known NAD-dependent deacetylase activity (Imai S-I, Armstrong CM, Kaeberlein M, Guarente L, Nature 403:795–800, 2000; Tanner KG, Landry J, Sternglanz R, Denu JM, Proc Natl Acad Sci U S A 97:14178–14182, 2000), the hydrolysis of succinyl and malonyl lysine on proteins. This finding suggested that other sirtuins (e.g. SIRT4, SIRT6, and SIRT7) with weak deacetylase activity may also prefer other acyl lysine modifications, which was confirmed later with several sirtuins. In this chapter, we will summarize what is known about SIRT5, with a focus on the discovery of its new enzymatic activity and how the new activity finding influences the understanding of SIRT5 function, inhibitor development, and the study of other sirtuins.
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Acknowledgements
Work in our laboratory on Sirt5 has been supported by NIH R01GM086703, R01CA163255, and R21NS073049.
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He, B., Lin, H. (2016). SIRT5 Reveals Novel Enzymatic Activities of Sirtuins. In: Houtkooper, R. (eds) Sirtuins. Proteins and Cell Regulation, vol 10. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0962-8_6
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DOI: https://doi.org/10.1007/978-94-024-0962-8_6
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