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Titolo:
Ectopic expression of Cdk6 circumvents transforming growth factor-beta mediated growth inhibition
Autore:
Zhang, F; Taipale, M; Heiskanen, A; Laiho, M;
Indirizzi:
Univ Helsinki, Mol Canc Biol Res Program, Dept Virol, Haartman Inst, FIN-00014 Helsinki, Finland Univ Helsinki Helsinki Finland FIN-00014 st, FIN-00014 Helsinki, Finland
Titolo Testata:
ONCOGENE
fascicolo: 41, volume: 20, anno: 2001,
pagine: 5888 - 5896
SICI:
0950-9232(20010913)20:41<5888:EEOCCT>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL-CYCLE ARREST; DEPENDENT KINASE INHIBITOR; TGF-BETA; EPITHELIAL-CELLS; MAMMALIAN-CELLS; P15(INK4B); PROTEIN; INK4; COMPLEXES; P27(KIP1);
Keywords:
TGF-beta; cyclin-dependent kinase; cyclin-dependent kinase inhibitors; cell cycle regulation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Laiho, M Univ Helsinki, Mol Canc Biol Res Program, Dept Virol, Haartman Inst, POB 63,Haartmaninkatu 8, FIN-00014 Helsinki, Finland Univ Helsinki POB 63,Haartmaninkatu 8 Helsinki Finland FIN-00014
Citazione:
F. Zhang et al., "Ectopic expression of Cdk6 circumvents transforming growth factor-beta mediated growth inhibition", ONCOGENE, 20(41), 2001, pp. 5888-5896

Abstract

Transforming growth factor-beta (TGF-beta) induced growth arrest of cells involves regulation of the activities of both D- and E-type cyclin kinase complexes thought to be mediated primarily by the regulation of p15(Ink4b) and p27(Kip1) cyclin kinase inhibitors. We show here that TGF-beta downregulates Cdk6 and that transient and stable expression of Cdk6 in Mv1Lu mink epithelial cells overrides TGF-beta mediated arrest. The main effect of the ectopic Cdk6 expression was to sequester TGF-P induced p15(Ink4b) and to maintain more p27(Kip1) in cyclin D-complexes preventing the complete shift ofp27(Kip1) to Cdk2 invoked by TGF-beta. This led to the presence of an active cyclinD-Cdk6-p27(Kip1) complex and partially active cyclin E-Cdk2 complex and resulted in the failure of TGF-beta to fully arrest Mv1Lu cell growth. Though dominant negative Cdk6, expressed similarly in the cells, sequestered both p15(Ink4b) and p27(Kip1), it lacks kinase activity and was unable to override the TGF-beta arrest. The results demonstrate that downregulation of Cdk6 kinase is required for the enforcement of the G(1)-phase arrest by TGF-beta and results in changes in association of the p15(Ink4b) and p27(Kip1) inhibitors with D- and E-type cyclin kinase complexes.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 21/09/20 alle ore 12:46:32