An integrated view of cyclin E function and regulation

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...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2012-01, Vol.11 (1), p.57-64
Main Authors: Siu, Ka Tat, Rosner, Marsha Rich, Minella, Alex C.
Format: Article
Language:English
Subjects:
Animals
Binding
Biology
Bioscience
Calcium
Cancer
Cell
Cell Cycle Proteins - genetics
Cell Cycle Proteins - metabolism
Cycle
Cyclin E - genetics
Cyclin E - metabolism
Cyclin-Dependent Kinase 2 - metabolism
Cyclin-Dependent Kinase Inhibitor p21 - antagonists & inhibitors
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
Cyclin-Dependent Kinase Inhibitor p27 - antagonists & inhibitors
Cyclin-Dependent Kinase Inhibitor p27 - metabolism
E2F Transcription Factors - metabolism
F-Box Proteins - genetics
F-Box Proteins - metabolism
F-Box-WD Repeat-Containing Protein 7
Gene Knock-In Techniques
Humans
Interphase
Landes
Mice
Organogenesis
Phosphorylation
Proteins
Substrate Specificity
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
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Description
Summary: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.
ISSN:1538-4101
1551-4005
DOI:10.4161/cc.11.1.18775