Modulation of pRb/E2F functions in the regulation of cell cycle and in cancer

Seville, Lucy L.; Shah, Nita; Westwell, Andrew D.; Chan, Weng C.

Abstract

Cell proliferation is regulated by the cell cycle, and in order to divide the cell must enter a mitotic state. Prior to mitosis the cell is required to pass through a number of checkpoints, including the critical G1/S restriction point governed by the successive phosphorylation of the retinoblastoma protein, pRb. The various proteins and regulatory factors governing pRb phosphorylation have been a major focus of study in recent years, given the central importance of G1/S transition deregulation in cancer development. This review summarises the molecular biology around the G1/S transition, focussing on the critical roles of the transcription factor family E2F and the cyclin-dependent kinase (CDK) and cyclin families involved in E2F release from pRb. Interestingly, E2F release from pRb is associated with cell proliferation; however, above a certain threshold E2F has the potential to trigger apoptosis. The review focuses on the following topics: (i) how E2F and other substrates bind to pRb at the molecular level; (ii) mechanisms by which pRb function is modulated within the cell; (iii) mechanisms that inhibit or enhance cell proliferation via the pRb/E2F pathway; (iv) how E2F can potentiate apoptotic pathways; and (v) what controls whether E2F mediates cell proliferation or apoptosis. The case for the development of agents that perturb pRb:E2F interactions will be made, as a strategy to further inform the molecular biology around this important target and as a therapeutic strategy against cancer. © 2005 Bentham Science Publishers Ltd.

Citation

Seville, L. L., Shah, N., Westwell, A. D., & Chan, W. C. (2005). Modulation of pRb/E2F functions in the regulation of cell cycle and in cancer. Current Cancer Drug Targets, 5(3), 159-170. https://doi.org/10.2174/1568009053765816

• Journal Article Type: Review
• Publication Date: May 1, 2005
• Deposit Date: Sep 10, 2020
• Journal: Current Cancer Drug Targets
• Print ISSN: 1568-0096
• Publisher: Bentham Science Publishers
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 3
• Pages: 159-170
• DOI: https://doi.org/10.2174/1568009053765816
• Public URL: https://nottingham-repository.worktribe.com/output/3137751
• Publisher URL: https://www.eurekaselect.com/60596/article