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].
References:
- [1]. Finnin MS, et al. Structure of the histone deacetylase SIRT2. Nat Struct Biol. 2001 Jul;8(7):621-5. [Content Brief]
- [2]. North BJ, et al. The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell. 2003 Feb;11(2):437-44. [Content Brief]
- [3]. Vaquero A, et al. SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev. 2006 May 15;20(10):1256-61. [Content Brief]
- [4]. Kim HS, et al. SIRT2 maintains genome integrity and suppresses tumorigenesis through regulating APC/C activity. Cancer Cell. 2011 Oct 18;20(4):487-99. [Content Brief]
- [5]. Outeiro TF, et al. Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science. 2007 Jul 27;317(5837):516-9. [Content Brief]
- [6]. Eldridge MJG, et al. Active nuclear import of the deacetylase Sirtuin-2 is controlled by its C-terminus and importins. Sci Rep. 2020 Feb 10;10(1):2034. [Content Brief]
- [7]. Piracha ZZ, et al. An Alternatively Spliced Sirtuin 2 Isoform 5 Inhibits Hepatitis B Virus Replication from cccDNA by Repressing Epigenetic Modifications Made by Histone Lysine Methyltransferases. J Virol. 2020 Jul 30;94(16):e00926-20. [Content Brief]
- [8]. Brady JJ, et al. An Arntl2-Driven Secretome Enables Lung Adenocarcinoma Metastatic Self-Sufficiency. Cancer Cell. 2016 May 9;29(5):697-710. [Content Brief]
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SIRT2 Related Products (64)
Related Products (64)
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Antibodies (1)
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A2B57
0 ImagesCat. No.: HY-117442CAS No.: 1602733-73-2A2B57 is a selective inhibitor for SIRT 2 with an IC50 of 6.3 µM.
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SIRT-IN-6
0 ImagesCat. No.: HY-W109401CAS No.: 1431411-18-5SIRT-IN-6 (Compound 14) is a pan-inhibitor of SIRT1/2/3 with IC50 values of >50 μM. SIRT-IN-6 is promising for research of metabolic, inflammatory, oncologic and neurodegenerative disorders.
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SIRT2-IN-18
0 ImagesCat. No.: HY-178773CAS No.: 858032-59-4SIRT2-IN-18 (Compound 8) is a SIRT2 inhibitor with IC50s of 5.3 and 12.3 μM for SmSIRT2 and hSIRT2, respectively. SIRT2-IN-18 shows potent antischistosomal activities against both Liberian and Puerto Rican strains of Schistosoma mansoni and reduces schistosomula and adult worm pair viability, pairing, and egg production, with low cytotoxicity in mammalian cells. SIRT2-IN-18 increases histone H3 hyperacetylation and induces cytochrome c-mediated apoptosis.
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A1B11
0 ImagesCat. No.: HY-119889CAS No.: 1602731-56-5A1B11 is a selective SIRT inhibitor (SIRT2:IC50=5.3 μM) that can be used in the study of neurodegenerative diseases.
