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

TLDR

p27 is a cyclin‑dependent kinase inhibitor that is degraded by the ubiquitin‑proteasome system in vivo and in vitro. The study investigates whether specific proteolysis of p27 regulates cyclin‑dependent kinase activity. Ubc2 and Ubc3 ubiquitinate p27, and reduced ubiquitination in quiescent cells increases p27 stability, showing that p27 abundance is controlled by proteasomal degradation.

Abstract

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.