SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion

Publication date: 28 March 2017
Source:Cell Reports, Volume 18, Issue 13
Author(s): Qiang Chen, Wenhui Hao, Cuiying Xiao, Ruihong Wang, Xiaoling Xu, Huiyan Lu, Weiping Chen, Chu-Xia Deng
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.

Graphical abstract

Teaser

Chen et al. demonstrate that SIRT6 is essential for adipogenesis by regulating mitotic clonal expansion. KIF5C is negatively regulated by SIRT6, and KIF5C is a negative regulator for adipogenesis by blocking CK2α′ nuclear translocation and CK2 kinase activity.


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