SIRT2

SIRT2 is an NAD⁺-dependent sirtuin deacetylase with a catalytic core containing a Rossmann-fold NAD-binding domain and a zinc-binding module^[1]. It functions as a cytoplasmic microtubule regulator by deacetylating α-tubulin Lys40 in vitro and in vivo, while SIRT2 knockdown causes tubulin hyperacetylation^[2]. Mechanistically, SIRT2 also enters chromatin-linked cell-cycle control, because it deacetylates histone H4K16 during G2/M and supports mitotic chromatin regulation^[3]. In cancer-relevant models, SIRT2 maintains genome integrity by deacetylating APC/C coactivators CDH1 and CDC20, and Sirt2 deficiency causes centrosome amplification, aneuploidy, and tumorigenesis in mice^[4]. In neurodegeneration models, SIRT2 inhibition rescues α-synuclein toxicity and modifies inclusion morphology in cellular Parkinson’s disease models^[5]. Compared with related sirtuin isoforms, SIRT2 shows distinctive cytoplasmic localization but undergoes active nuclear import controlled by its C-terminus and importins^[6]. Isoform-level analysis is important because catalytically inactive nuclear SIRT2.5 antagonizes SIRT2.1 and SIRT2.2 effects on HBV replication from cccDNA^[7]. For experimental applications, SIRT2 inhibitors support studies of microtubule acetylation, mitotic regulation, α-synuclein toxicity, viral chromatin control, and Myc-driven cancer signaling^{[2][4][5][7][8]}.