title: Cables1 Inhibits Proliferation and Induces Senescence by Angiotensin II via a p21-Dependent Pathway in Human Umbilical Vein Endothelial Cells.
abstract: 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.
authors.affiliation: Department of Cardiology, 2nd Affiliated Hospital, and Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, China.
authors.forename: Zhongyue
authors.initials: Z
authors.lastname: Pu
authors.forename: Yongshun
authors.initials: Y
authors.lastname: Wang
authors.forename: Xinxin
authors.initials: X
authors.lastname: Liu
authors.forename: Jingjin
authors.initials: J
authors.lastname: Liu
authors.forename: Jinjin
authors.initials: J
authors.lastname: Cui
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Lv
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
chemical_list: C486568:CABLES1 protein, human; C493956:CDKN1A protein, human; D002352:Carrier Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D010750:Phosphoproteins; D000804:Angiotensin II