Downregulation of cyclin-dependent kinase inhibitor; p57{sup kip2}, is involved in the cell cycle progression of vascular smooth muscle cells
- Department of Cardiovascular Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638 (Japan)
- 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, Vol. 338, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2005.10.093; PII: S0006-291X(05)02344-2; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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