Abstract
Sirtuin 2 (SIRT2) is a member of the sirtuin protein family. It is a Class III histone deacetylase (HDACs) and predominantly localized to the cytosol. SIRT2 deacetylates histones and a number of non-histone proteins and plays a pivotal role in various physiologic processes. Previously, SIRT2 has been considered indispensable during carcinogenesis; however, there is now a significant controversy regarding whether SIRT2 is an oncogene or a tumor suppressor. The purpose of this review is to summarize the physiological functions of SIRT2 and its mechanisms in cancer. We will focus on five malignancies (breast cancer, non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, and glioma) to describe the current status of SIRT2 research and discuss the clinical evaluation of SIRT2 expression and the use of SIRT2 inhibitors.
Highlights
Posttranslational modifications fine tune the biological activity of many proteins [1, 2]
Many new substrates and Sirtuin 2 (SIRT2)-related proteins had been identified, such as CDK9, PGAM2, Par-3, and CDH1/CDC20, etc. (Table 1) [13,14,15,16,17,18,19,20,21,22,23,24,25]. These results suggest that SIRT2 regulates multiple biological functions, including neurotoxicity, metabolism, mitosis regulation, genome integrity, oxidative stress, and autophagy (Table 1)
Inconsistent results from clinical studies raise the utility of SIRT2 expression as a biomarker
Summary
Posttranslational modifications fine tune the biological activity of many proteins [1, 2]. Sirtuins are protein deacetylases, including a family of proteins (SIRT1–7) with homology to the silent information regulator 2 (Sir2) gene in Saccharomyces cerevisiae [4, 5]. This family of proteins contains highly conserved enzymes categorized as Class III histone deacetylases (HDACs III), and their deacetylase activity is dependent on nicotinamide adenine dinucleotide (NAD) as a cofactor distinct from zincdependent HDACs [6, 7]. Sirtuin 2 (SIRT2) is the only sirtuin predominantly found in the cell cytoplasm [7]; it can shuttle in and out of its primary location, using mechanisms which may be cell and tissue dependent [8, 12]. There is growing evidence that abnormal expression of SIRT2 is primarily associated with two human diseases, neurologic diseases, and cancer
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