An integrated view of cyclin E function and regulation |
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Authors: | Ka Tat Siu Marsha Rich Rosner Alex C Minella |
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Affiliation: | 1.Department of Medicine; Hematology/Oncology Division; Integrated Graduate Program in the Life Sciences; Feinberg School of Medicine; Northwestern University; Chicago, IL USA;2.Robert H. Lurie Comprehensive Cancer Center; Chicago, IL USA;3.Ben May Department of Cancer Research; Gordon Center for Integrative Sciences; The University of Chicago; Chicago, IL USA |
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Abstract: | Cancers of diverse cell lineages express high levels of cyclin E, and in various studies, cyclin E overexpression correlates with increased tumor aggression. One way that normal control of cyclin E expression is disabled in cancer cells is via loss-of-function mutations sustained by FBXW7. This gene encodes the Fbw7 tumor suppressor protein that provides substrate specificity for a ubiquitin ligase complex that targets multiple oncoproteins for degradation. Numerous other mechanisms besides Fbw7 mutations can deregulate cyclin E expression and activity in cancer cells. Recent reports demonstrate that inappropriate cyclin E expression may have far-reaching biological consequences for cell physiology, including altering gene expression programs governing proliferation, differentiation, survival and senescence. In this Perspective, we discuss the function of mammalian cyclin E in the context of these new data as well as the complex network that connects cyclin E functions to the cellular controls regulating its expression and activity.Key words: cell cycle, cyclin E, Cdk2, Fbw7, E2F, p21, p27, regulatory network |
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