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Interplay Between Cyclin-Dependent Kinases and E2F-Dependent Transcription

  • Jun-Yuan Ji
  • Nicholas J. Dyson
Chapter
Part of the Current Cancer Research book series (CUCR)

Abstract

Precise control of cell proliferation is essential for normal development and survival of all multi-cellular organisms. The deregulation of cell proliferation is a fundamental feature of all types of cancer. One of the key regulators of cell proliferation is the E2F transcription factor. E2F controls the expression of many genes that are required for cells to divide and elevated E2F activity is found in most tumor cells. The activation and inactivation of E2F are tightly linked to the activation of cyclin-dependent kinases (CDKs). In normal cells, these connections allow the periodic oscillations in CDK cycle to be coupled with temporal programs of gene expression. Multiple CDK–cyclin complexes (including CDK1/2–CycA, CDK1/2–CycB, and CDK7–CycH) have been shown to directly phosphorylate E2F or its dimerization partner DP. However, in recent genetic studies, one of the strongest modifiers of E2F-dependent phenotypes was cdk8, a kinase that had not previously been linked to E2F. In this review, we summarize the effects of CDKs on E2F1 activity and describe a model that may explain the role of CDK8–CycC in E2F regulation. Since CDKs can both increase and decrease E2F activity, understanding the interplay between E2F and CDK–cyclin complexes may suggest therapeutic approaches to efficiently block cancer cell proliferation.

Keywords

Mediator Complex CDK8 Module Cyclin Complex Drive Cell Cycle Progression Transcriptional Oscillator 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

We thank Drs. Erick Morris, Gerold Schubiger, and Fajun Yang for critical comments on this review. J.Y.J. is supported by a post-doctoral fellowship from the MGH Fund for Medical Discovery. This work was supported by a grant from the NIH (RO1 GM53203). N.J.D. is the MGH Saltonstall Foundation Scholar.

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of PathologyHarvard Medical School, Massachusetts General Hospital Cancer CenterCharlestownUSA
  2. 2.Department of Molecular and Cellular MedicineTexas A&M Health Science CenterCollege StationUSA

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