title: SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion.
abstract: 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.
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Hao
authors.affiliation: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Cuiying
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Ruihong
authors.initials: R
authors.lastname: Wang
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau SAR, China, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xu
authors.affiliation: Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Huiyan
authors.initials: H
authors.lastname: Lu
authors.affiliation: Genomic Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Chen
authors.affiliation: 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. Electronic address: cxdeng@umac.mo.
authors.forename: Chu-Xia
authors.initials: CX
authors.lastname: Deng
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis; D000818:Animals; D047390:Casein Kinase II / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D002999:Clone Cells; D017353:Gene Deletion; D016547:Kinesins / Q000378:metabolism; D051379:Mice; D008938:Mitosis; D010641:Phenotype; D021381:Protein Transport; D037761:Sirtuins / Q000172:deficiency / Q000378:metabolism*
chemical_list: C501860:Sirt6 protein, mouse; D047390:Casein Kinase II; D037761:Sirtuins; C000599520:KIF5C protein, mouse; D016547:Kinesins
keywords: CK2; KIF5C; SIRT6; adipogenesis; mitotic clonal expansion