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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Cycle Proteins / genetics
-
Cell Cycle Proteins / metabolism
-
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
-
Mice
-
Phosphorylation
-
Substrate Specificity
-
Ubiquitin-Protein Ligases / genetics
-
Ubiquitin-Protein Ligases / metabolism
Substances
-
Cell Cycle Proteins
-
Cyclin E
-
Cyclin-Dependent Kinase Inhibitor p21
-
E2F Transcription Factors
-
F-Box Proteins
-
F-Box-WD Repeat-Containing Protein 7
-
FBXW7 protein, human
-
Cyclin-Dependent Kinase Inhibitor p27
-
Ubiquitin-Protein Ligases
-
Cyclin-Dependent Kinase 2