Department of Microbiology & Molecular Biology, College of Biological Science and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
Department of Microbiology & Molecular Biology, College of Biological Science and Biotechnology, Chungnam National University, Daejeon 34134, Republic of Korea.
Biochim Biophys Acta Mol Cell Res. 2018 Sep;1865(9):1230-1238. doi: 10.1016/j.bbamcr.2018.06.005. Epub 2018 Jun 14.
SIRT2, a member of the class III histone deacetylase family, has been identified as a tumor suppressor, which is associated with various cellular processes including metabolism and proliferation. However, the effects of SIRT2 on cancer cell migration caused by cytoskeletal rearrangement remain uncertain. Here we show that SIRT2 inhibits cell motility by suppressing actin polymerization. SIRT2 regulates actin dynamics through HSP90 destabilization and subsequent repression of LIM kinase (LIMK) 1/cofilin pathway. SIRT2 directly interacts with HSP90 and regulates its acetylation and ubiquitination. In addition, the deacetylase activity of SIRT2 is required for the regulation of actin polymerization and the ubiquitin-mediated proteasomal degradation of HSP90 induced by SIRT2.
SIRT2 是 III 类组蛋白去乙酰化酶家族的成员，已被鉴定为一种肿瘤抑制因子，与包括代谢和增殖在内的各种细胞过程有关。然而，SIRT2 对细胞骨架重排引起的癌细胞迁移的影响尚不确定。在这里，我们表明 SIRT2 通过抑制肌动蛋白聚合来抑制细胞迁移。SIRT2 通过 HSP90 失稳和随后抑制 LIM 激酶 (LIMK) 1/丝切蛋白途径来调节肌动蛋白动力学。SIRT2 直接与 HSP90 相互作用并调节其乙酰化和泛素化。此外，SIRT2 的去乙酰化酶活性对于 SIRT2 诱导的肌动蛋白聚合和 HSP90 的泛素介导的蛋白酶体降解的调节是必需的。
