期刊
JOURNAL OF VASCULAR RESEARCH
卷 54, 期 1, 页码 13-21出版社
KARGER
DOI: 10.1159/000452409
关键词
Senescence; Proliferation; Endothelial cells; Cables1; p21
资金
- Key Program of the National Natural Science Foundation of China [81330033]
- National Natural Science Funds for Young Scholars [81400296]
- Heilongjiang Province Foundation for Returnees [LC201434]
- Key Laboratory of Myocardial Ischemia (Harbin Medical University)
- Ministry of Education [KF201510]
Cables1 (Cdk5 and Abl enzyme substrate 1) is a vital cell cycle regulator and a candidate tumor suppressor that negatively regulates cell growth by inhibiting cyclin-dependent kinases. Here, we report on the critical role of the Cables1/p21 pathway, which inhibits cell proliferation and induces cell senescence in human umbilical vein endothelial cells. Moreover, we confirmed that silencing of Cables1 promoted cell proliferation as well as increased resistance to angiotensin II-induced senescence, at least in part, by altering Cables1 activation. We further demonstrated that knockdown of p21 reverses Cables1-mediated cell growth inhibition and cell senescence. Taken together, these results suggest that the Cables1/p21 pathway has a strong effect on the induction of cell senescence and inhibition of cell growth, and acts as a novel regulatory mechanism in which p21 is probably one of several downstream effector molecules to mediate Cables1. (C) 2017 S. Karger AG, Basel
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