Genetic Analysis of Mammalian Cyclin-Dependent Kinases and Their Inhibitors
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Marcos Malumbres
Abstract
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.
Copyright © 2000 by Walter de Gruyter GmbH & Co. KG
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Articles in the same Issue
- Alexander J. Varshavsky Felix Hoppe-Seyler Lecturer 2000
- The Ubiquitin System and the N-End Rule Pathway
- Paper of the Year 1999: Award to Igor Stagljar
- A Clockwork Organ
- The Transgeneticists Toolbox: Novel Methods for the Targeted Modification of Eukaryotic Genomes
- Interdependence of Filamentous Actin and Microtubules for Asymmetric Cell Division
- Genetic Analysis of Mammalian Cyclin-Dependent Kinases and Their Inhibitors
- Phosphorylcholine Substituents in Nematodes: Structures, Occurrence and Biological Implications
- Selenium in Biology: Facts and Medical Perspectives
- The Role of Se, Mo and Fe in the Structure and Function of Carbon Monoxide Dehydrogenase
- Molecular Basis for Interactions of the DnaK Chaperone with Substrates
- Protein Import: the Hitchhikers Guide into Chloroplasts
- Pathway Analysis and Metabolic Engineering in Corynebacterium glutamicum
- Metabolic Networks: a Signal-Oriented Approach to Cellular Models
- Representing and Analysing Molecular and Cellular Function Using the Computer
- Protein Aggregation and Pathogenesis of Huntingtons Disease: Mechanisms and Correlations
- The Mitochondrial Protein Import Motor
- The Immunoglobulin κ Gene Families of Human and Mouse: a Cottage Industry Approach
- Protein-Protein Interactions in Receptor Activation and Intracellular Signalling
- Molecular Genetic Analysis of Glucocorticoid Signaling Using the Cre/loxP System
- Macromolecular Intelligence in Microorganisms
- Thyroid Hormone Receptors Bind to an Element in the Connexin43 Promoter
- Analysis of the Deubiquitinating Enzymes of the Yeast Saccharomyces cerevisiae
- Helical Tubes of FtsZ from Methanococcus jannaschii
- Surface Topography of Microtubule Walls Decorated with Monomeric and Dimeric Kinesin Constructs
- Histone Deacetylase Activity Is Required for the Induction of the MyoD Muscle Cell Lineage in Xenopus
- The Effect of Heat Shock on 20S/26S Proteasomes
- Sec61p Is the Main Ribosome Receptor in the Endoplasmic Reticulum of Saccharomyces cerevisiae
