This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DuPree, E. L. Articles by Almasan, A. Search for Related Content PubMed PubMed Citation Articles by DuPree, E. L. Articles by Almasan, A.

Genotoxic Stress Induces Expression of E2F4, Leading to Its Association with p130 in Prostate Carcinoma Cells

Departments of ¹ Cancer Biology and ² Radiation Oncology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, and ³ Department of Chemistry, Cleveland State University, Cleveland, Ohio

The retinoblastoma (pRb), p107, and p130 pocket proteins bind to the E2F transcription factors to control gene expression. E2F4 protein levels increased and accumulated in the nuclei of prostate carcinoma cells subjected to ionizing radiation (IR). The IR-induced increase of E2F4 levels led to an increase in E2F4 binding to p130 but had no effect on E2F4/p107 or E2F5/p130 complexes. The increase in E2F4/p130 association after IR was observed in prostate carcinoma cells regardless of their sensitivity to androgens, but not in breast carcinoma cells. E2F4/p130 complex formation was dependent on dissociation of p130 from cyclin-dependent kinase 2 and p130 dephosphorylation. Disruption of E2F4 through small interfering RNA prevented p130/E2F4 complex formation and sensitized cells to IR-induced apoptosis, leading to caspase-3 activation, cleavage of its substrate, poly(ADP-ribose) polymerase, and nuclear condensation. The E2F4/p130 pocket protein complex emerges as a new target of radiation in prostate carcinoma cells.

This article has been cited by other articles:

				Y. Ma, C. A. Kurtyka, S. Boyapalle, S.-S. Sung, H. Lawrence, W. Guida, and W. D. Cress A Small-Molecule E2F Inhibitor Blocks Growth in a Melanoma Culture Model Cancer Res., August 1, 2008; 68(15): 6292 - 6299. [Abstract] [Full Text] [PDF]

				S. A. Amundson, K. T. Do, L. C. Vinikoor, R. A. Lee, C. A. Koch-Paiz, J. Ahn, M. Reimers, Y. Chen, D. A. Scudiero, J. N. Weinstein, et al. Integrating Global Gene Expression and Radiation Survival Parameters across the 60 Cell Lines of the National Cancer Institute Anticancer Drug Screen Cancer Res., January 15, 2008; 68(2): 415 - 424. [Abstract] [Full Text] [PDF]

				S. Ray, S. Shyam, G. C. Fraizer, and A. Almasan S-phase checkpoints regulate Apo2 ligand/TRAIL and CPT-11-induced apoptosis of prostate cancer cells Mol. Cancer Ther., April 1, 2007; 6(4): 1368 - 1378. [Abstract] [Full Text] [PDF]

				R. S. Bindra, S. L. Gibson, A. Meng, U. Westermark, M. Jasin, A. J. Pierce, R. G. Bristow, M. K. Classon, and P. M. Glazer Hypoxia-Induced Down-regulation of BRCA1 Expression by E2Fs Cancer Res., December 15, 2005; 65(24): 11597 - 11604. [Abstract] [Full Text] [PDF]