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Downregulation of cyclin-dependent kinase inhibitor; p57{sup kip2}, is involved in the cell cycle progression of vascular smooth muscle cells

Journal Article · · Biochemical and Biophysical Research Communications
DOI:https://doi.org/10.1016/J.BBRC.2005.1· OSTI ID:20793239
 [1];  [1];  [1];  [1];  [1];  [2];  [2];  [1];  [2];  [1]
  1. Department of Cardiovascular Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638 (Japan)
  2. Division of Molecular Oncology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815 (Japan)
Immature vascular smooth muscle cells (VSMCs) proliferate responding to extrinsic mitogens and accumulate in neointima after arterial injuries. Cell proliferation is positively regulated by cyclin/cyclin-dependent kinase (CDK) complex and negatively controlled by CDK inhibitors; CKIs such as p27{sup kip1} and p57{sup kip2}. In this study, embryonic rat thoracic aorta VSMCs; A10 were G0/G1 arrested by serum starvation, re-stimulated with serum, and harvested every four hours. Both CKIs co-expressed in quiescent VSMCs and rapidly diminished by stimulation. Protein level of p27{sup kip1} was regulated by both transcription and post-transcription, but that of p57{sup kip2} was mainly by post-transcription. Supplemental overexpression of p57{sup kip2} inhibited the activations of G1 cyclin/CDKs and subsequent hyperphosphorylations of all three retinoblastoma pocket proteins as well as G1/S transition of cell cycle. Our findings suggest that the downregulations of not only p27{sup kip1}, but also p57{sup kip2} responding to mitogenic stimulation, play key roles in the cell cycle progression of VSMCs.
OSTI ID:
20793239
Journal Information:
Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 338; ISSN 0006-291X; ISSN BBRCA9
Country of Publication:
United States
Language:
English

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