title: An integrated view of cyclin E function and regulation.
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 review, 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.
authors.affiliation: Department of Medicine, Hematology/Oncology Division, Integrated Graduate Program in the Life Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Ka Tat
authors.initials: KT
authors.lastname: Siu
authors.forename: Marsha Rich
authors.initials: MR
authors.lastname: Rosner
authors.forename: Alex C
authors.initials: AC
authors.lastname: Minella
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000037:antagonists & inhibitors / Q000378:metabolism; D050684:E2F Transcription Factors / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D000073979:F-Box-WD Repeat-Containing Protein 7; D055879:Gene Knock-In Techniques; D006801:Humans; D007399:Interphase; D051379:Mice; D010766:Phosphorylation; D013379:Substrate Specificity; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050684:E2F Transcription Factors; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513273:FBXW7 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D044767:Ubiquitin-Protein Ligases; D051357:Cyclin-Dependent Kinase 2