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Marcos Malumbres, Sagrario Ortega, Mariano Barbacid

Genetic Analysis of Mammalian Cyclin-Dependent Kinases and Their Inhibitors

Entry into the cell cycle, in particular the G1/S transition, is a tightly regulated process that involves a combination of mitogenic signaling pathways and cell cycle checkpoints. Some of the key regulators of this process are frequently altered in human cancer. Although the proteins that control the G1/S transition have been extensively studied at the biochemical level, little is known regarding their physiological role in vivo. During the last few years, a series of mouse strains carrying gene targeted mutations in key regulators of the G1/S transition have been generated. They include the Rb family of proteins and some of their downstream and upstream regulators. The latter include the regulatory (cyclin) and catalytic (Cdk) sub-units of some of the kinases responsible for Rb inactivation as well as all the members of two families of cell cycle inhibitors, the INK4 and the Cip/Kip proteins. In this review, we summarize the most relevant information derived from the characterization of these strains of mice and attempt to integrate it within a functional framework of cell cycle regulation in vivo.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 381, 09/2000
Pages: 827 - 838

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