title: Regulation of the cyclin-dependent kinase inhibitor p27 by degradation and phosphorylation.
abstract: The cell cycle has been the object of extensive studies for the past years. A complex network of molecular interactions has been identified. In particular, a class of cell cycle inhibitory proteins has been cloned and characterized but details of the molecular mechanism of their action have yet to be resolved. These inhibitors regulate the progression through G1 and the G1/S transition via the inhibition of the cyclin-dependent kinase (Cdk) activity. The potential function of these negative regulators as tumor suppressors provides new insights into the link between the cell cycle and oncogenesis. p27 is a potent inhibitor of Cdks. In quiescent cells p27 accumulates without an increase in mRNA or protein synthesis. Cell cycle regulation of p27 levels, both in normal and transformed human cells, occurs via the ubiquitin-proteasome pathway and, compared to proliferating cells, quiescent cells contain a far lower amount of p27 ubiquitinating activity. The specific proteolysis of p27 is probably involved in the pathway of activation of Cdks. p27 is a phosphoprotein and its phosphorylation is cell cycle regulated. Often phosphorylation is a signal for ubiquitination. p27 is phosphorylated exclusively on serine by Erk1 and almost exclusively on threonine by Cdk1 in in vitro experiments. This finding raises the question of whether and how phosphorylation by these kinases is involved in the process of p27 proteolysis.
authors.affiliation: Renal Unit, Massachusetts General Hospital East, USA.
authors.forename: A
authors.initials: A
authors.lastname: Alessandrini
authors.forename: D S
authors.initials: DS
authors.lastname: Chiaur
authors.forename: M
authors.initials: M
authors.lastname: Pagano
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011506:Proteins; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27