title: AS160 controls eukaryotic cell cycle and proliferation by regulating the CDK inhibitor p21.
abstract: AS160 (TBC1D4) has been implicated in multiple biological processes. However, the role and the mechanism of action of AS160 in the regulation of cell proliferation remain unclear. In this study, we demonstrated that AS160 knockdown led to blunted cell proliferation in multiple cell types, including fibroblasts and cancer cells. The results of cell cycle analysis showed that these cells were arrested in the G1 phase. Intriguingly, this inhibition of cell proliferation and the cell cycle arrest caused by AS160 depletion were glucose independent. Moreover, AS160 silencing led to a marked upregulation of the expression of the cyclin-dependent kinase inhibitor p21. Furthermore, whereas AS160 overexpression resulted in p21 downregulation and rescued the arrested cell cycle in AS160-depeleted cells, p21 silencing rescued the inhibited cell cycle and proliferation in the cells. Thus, our results demonstrated that AS160 regulates glucose-independent eukaryotic cell proliferation through p21-dependent control of the cell cycle, and thereby revealed a molecular mechanism of AS160 modulation of cell cycle and proliferation that is of general physiological significance.
authors.affiliation: a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan , P.R. China.|b Graduate University of Chinese Academy of Sciences , Beijing , P.R. China.
authors.forename: Pianchou
authors.initials: P
authors.lastname: Gongpan
authors.affiliation: a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan , P.R. China.|b Graduate University of Chinese Academy of Sciences , Beijing , P.R. China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Lu
authors.affiliation: a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan , P.R. China.|b Graduate University of Chinese Academy of Sciences , Beijing , P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan , P.R. China.|b Graduate University of Chinese Academy of Sciences , Beijing , P.R. China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Xu
authors.affiliation: a State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany , Chinese Academy of Sciences , Kunming , Yunnan , P.R. China.
authors.forename: Wenyong
authors.initials: W
authors.lastname: Xiong
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D020868:Gene Silencing / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology; D051379:Mice; D034741:RNA, Small Interfering / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D020690:GTPase-Activating Proteins; D034741:RNA, Small Interfering; C518767:TBC1D4 protein, human; C505647:Tbc1d4 protein, mouse; D019344:Lactic Acid; D005947:Glucose
keywords: AS160/TBC1D4; G1/S; cell cycle; cell proliferation; p21