Ubiquitin-mediated proteolysis of vertebrate G1- and S-phase regulators.
Cell-cycle progression in all eukaryotes is driven by cyclin-dependent kinases (CDKs) and their cyclin partners. In vertebrates, the proper and timely duplication of the genome during S-phase relies on the coordinated activities of positive regulators such as CDK-cyclins and E2F, and negative regulators such as CDK inhibitors of the Cip/Kip and INK4 families. Recent and ongoing work indicates that many important regulators of G1- and S-phases are targeted for ubiquitination and subsequent degradation by the 26S proteasome. The proteolysis of key proteins during G1- and S-phases appears to be central for proper custodial regulation of DNA replication and the maintenance of cellular homeostasis in general. This review highlights the current literature regarding ubiquitin-mediated proteolysis of G1- and S-phase regulators and the control of events during the initiation and completion of DNA replication in vertebrates.
Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207, USA. yew@uthscsa.edu
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D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004261:DNA Replication; D016193:G1 Phase; D016196:S Phase; D014452:Ubiquitins / Q000502:physiology*; D015003:Yeasts / Q000378:metabolism
D018797:Cell Cycle Proteins; D016213:Cyclins; D014452:Ubiquitins; D018844:Cyclin-Dependent Kinases