Cyclin B1 and CDK1: nuclear localization and upstream regulators.
Formation of an active nuclear cyclin B1-CDK1 complex is a highly intricate procedure requiring many different levels of regulation. Each of these regulatory steps represents a potential target for controlling cell proliferation. Accumulation of threshold levels of cyclin B1 protein at the G2/M transition requires the cooperation of various promoter elements, possibly the activation of several transcription factors, enhanced cyclin B1 mRNA stability and, in some cases, translational activation of dormant mRNA. Binding of cyclin B1 to its inactive partner, CDK1, initiates conformational changes allowing CDK1 to alter its phosphorylation status and to become an active kinase. Lastly, the active cyclin B1-CDK1 complex must translocate to the nucleus to begin phosphorylating nuclear substrates. These phosphorylation events are necessary for mitotic onset. While cyclin B1 is capable of shuttling from the nucleus to the cytoplasm throughout interphase, mitotic onset requires phosphorylation of cyclin B1 within the CRS region, thereby enhancing import and inhibiting export of the cyclin B1-CDK1 complex. Elucidating the role of mediators controlling cyclin B1-CDK1 translocation at the onset of mitosis is essential in developing drug targets for cell cycle control.
Porter
Lisa A
LA
Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093-0367, USA.
Donoghue
Daniel J
DJ
D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016203:CDC2 Protein Kinase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D019926:Cyclin B / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D056744:Cyclin B1; D004353:Drug Evaluation, Preclinical; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D016203:CDC2 Protein Kinase