title: Downregulation of cyclin-dependent kinase inhibitor; p57(kip2), is involved in the cell cycle progression of vascular smooth muscle cells.
abstract: 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(kip1) and p57(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(kip1) was regulated by both transcription and post-transcription, but that of p57(kip2) was mainly by post-transcription. Supplemental overexpression of p57(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(kip1), but also p57(kip2) responding to mitogenic stimulation, play key roles in the cell cycle progression of VSMCs.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan. norida@med.hokudai.ac.jp
authors.forename: Noritsugu
authors.initials: N
authors.lastname: Nakano
authors.forename: Kazushi
authors.initials: K
authors.lastname: Urasawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takagi
authors.forename: Takahiko
authors.initials: T
authors.lastname: Saito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kaneta
authors.forename: Susumu
authors.initials: S
authors.lastname: Ishikawa
authors.forename: Hideaki
authors.initials: H
authors.lastname: Higashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Masanori
authors.initials: M
authors.lastname: Hatakeyama
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D056746:Cyclin G; D056766:Cyclin G1; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D015536:Down-Regulation; D015971:Gene Expression Regulation, Enzymologic; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D044967:Serum
chemical_list: C534704:Ccng1 protein, rat; D056746:Cyclin G; D056766:Cyclin G1; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; D012333:RNA, Messenger