SIRT6通过调节有丝分裂克隆扩增对脂肪细胞分化至关重要。
SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion.
作者信息
Chen Qiang, Hao Wenhui, Xiao Cuiying, Wang Ruihong, Xu Xiaoling, Lu Huiyan, Chen Weiping, Deng Chu-Xia
机构信息
Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
出版信息
Cell Rep. 2017 Mar 28;18(13):3155-3166. doi: 10.1016/j.celrep.2017.03.006.
Preadipocytes initiate differentiation into adipocytes through a cascade of events. Mitotic clonal expansion, as one of the earliest events, is essential for adipogenesis. However, the underlying mechanisms that regulate mitotic clonal expansion remain elusive. SIRT6 is a member of the evolutionarily conserved sirtuin family of nicotinamide adenine dinucleotide (NAD)+-dependent protein deacetylases. Here, we show that SIRT6 deficiency in preadipocytes blocks their adipogenesis. Analysis of gene expression during adipogenesis reveals that KIF5C, which belongs to the kinesin family, is negatively regulated by SIRT6. Furthermore, we show that KIF5C is a negative factor for adipogenesis through interacting with CK2α', a catalytic subunit of CK2. This interaction blocks CK2α' nuclear translocation and CK2 kinase activity and inhibits mitotic clonal expansion during adipogenesis. These findings reveal a crucial role of SIRT6 in adipogenesis and provide potential therapeutic targets for obesity.
前脂肪细胞通过一系列事件启动向脂肪细胞的分化。有丝分裂克隆扩增作为最早的事件之一，对脂肪生成至关重要。然而，调节有丝分裂克隆扩增的潜在机制仍然不清楚。SIRT6是烟酰胺腺嘌呤二核苷酸（NAD）+依赖性蛋白脱乙酰酶的进化保守的沉默调节蛋白家族的成员。在这里，我们表明前脂肪细胞中SIRT6的缺乏会阻止它们的脂肪生成。对脂肪生成过程中基因表达的分析表明，属于驱动蛋白家族的KIF5C受SIRT6负调控。此外，我们表明KIF5C通过与CK2的催化亚基CK2α'相互作用而成为脂肪生成的负因子。这种相互作用阻断了CK2α'的核转位和CK2激酶活性，并抑制了脂肪生成过程中的有丝分裂克隆扩增。这些发现揭示了SIRT6在脂肪生成中的关键作用，并为肥胖症提供了潜在的治疗靶点。
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