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.
Yew
P R
PR
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
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