SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion

Qiang Chen; Wenhui Hao; Cuiying Xiao; Ruihong Wang; Xiaoling Xu; Huiyan Lu; Weiping Chen; Chu-Xia Deng

doi:10.1016/j.celrep.2017.03.006

Cell Reports (Mar 2017)

SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion

Qiang Chen,
Wenhui Hao,
Cuiying Xiao,
Ruihong Wang,
Xiaoling Xu,
Huiyan Lu,
Weiping Chen,
Chu-Xia Deng

Affiliations

Qiang Chen: Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
Wenhui Hao: Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
Cuiying Xiao: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
Ruihong Wang: Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
Xiaoling Xu: Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
Huiyan Lu: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
Weiping Chen: Genomic Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
Chu-Xia Deng: Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA

DOI: https://doi.org/10.1016/j.celrep.2017.03.006
Journal volume & issue: Vol. 18, no. 13
pp. 3155 – 3166

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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