Role of the Ubiquitin-Proteasome Pathway in Regulating Abundance of the Cyclin-Dependent Kinase Inhibitor p27

American Association for the Advancement of Science (AAAS) - Tập 269 Số 5224 - Trang 682-685 - 1995
Michele Pagano1, Sun W. Tam1, Anne M. Theodoras1, Peggy Beer‐Romero1, Giannino Del Sal1, Vincent Chau2, P. Renée Yew3, Giulio Draetta1, Mark Rolfe1
1Mitotix Inc., Cambridge, MA 02139, USA
2Department of Pharmacology, Wayne State University, Detroit, MI 48201, USA
3Department of Cell Biology, Harvard Medical School, Boston, MA 02115 USA

Tóm tắt

The p27 mammalian cell cycle protein is an inhibitor of cyclin-dependent kinases. Both in vivo and in vitro, p27 was found to be degraded by the ubiquitin-proteasome pathway. The human ubiquitin-conjugating enzymes Ubc2 and Ubc3 were specifically involved in the ubiquitination of p27. Compared with proliferating cells, quiescent cells exhibited a smaller amount of p27 ubiquitinating activity, which accounted for the marked increase of p27 half-life measured in these cells. Thus, the abundance of p27 in cells is regulated by degradation. The specific proteolysis of p27 may represent a mechanism for regulating the activity of cyclin-dependent kinases.

Từ khóa


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