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Cell Cycle. 2016 Jul 2;15(13):1733-41. doi: 10.1080/15384101.2016.1183853. Epub 2016 May 6.

AS160 controls eukaryotic cell cycle and proliferation by regulating the CDK inhibitor p21.

Gongpan P1,2, Lu Y1,2, Wang F1,2, Xu Y1,2, Xiong W1.

Author information

1
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.
2
b Graduate University of Chinese Academy of Sciences , Beijing , P.R. China.

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.

KEYWORDS:

AS160/TBC1D4; G1/S; cell cycle; cell proliferation; p21

PMID:
27152871
PMCID:
PMC4957568
DOI:
10.1080/15384101.2016.1183853
[Indexed for MEDLINE]
Free PMC Article

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