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 Wang, S.-C. Articles by Hung, M.-C. Search for Related Content PubMed PubMed Citation Articles by Wang, S.-C. Articles by Hung, M.-C.

Ultraviolet Irradiation Induces BRCA2 Protein Depletion through a p53-independent and Protein Synthesis-dependent Pathway¹

Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

It has been suggested that BRCA2, the protein product of the breast cancer susceptibility gene BRCA2, is involved in DNA damage repair. It is therefore likely that BRCA2 plays a role in a signaling pathway induced by DNA-damaging agents. To test this possibility, we examined the alteration of the BRCA2 protein level in human cell lines after UV irradiation. We found that UV irradiation down-regulated BRCA2 in a dose-dependent manner in all cell lines tested. The down-regulation of BRCA2 occurred soon (within 4 h) after UV treatment. Surprisingly, down-regulation of BRCA2 by UV does not require functional p53, which has been suggested to be required for the down-regulation of BRCA1 and BRCA2 mRNAs by DNA-damaging agents. Moreover, the proteosome- and calpain-mediated protein degradation pathways do not have an important role in the UV-induced BRCA2 depletion. However, blocking protein synthesis temporally inhibited the depletion of BRCA2 and BRCA1 in some cell lines. Ectopic expression of BRCA2 in cells increased resistance of cells to high-dose UV irradiation. These results demonstrate that BRCA2 is involved in a DNA-damaging signaling pathway induced by UV radiation and that expression of BRCA2 can protect cells from UV-mediated cell death.

This article has been cited by other articles:

				L. Moro, A. A. Arbini, E. Marra, and M. Greco Down-regulation of BRCA2 Expression by Collagen Type I Promotes Prostate Cancer Cell Proliferation J. Biol. Chem., June 10, 2005; 280(23): 22482 - 22491. [Abstract] [Full Text] [PDF]

				A. R. Schoenfeld, S. Apgar, G. Dolios, R. Wang, and S. A. Aaronson BRCA2 Is Ubiquitinated In Vivo and Interacts with USP11, a Deubiquitinating Enzyme That Exhibits Prosurvival Function in the Cellular Response to DNA Damage Mol. Cell. Biol., September 1, 2004; 24(17): 7444 - 7455. [Abstract] [Full Text] [PDF]

				F. Liu, M. Dowling, X.-J. Yang, and G. D. Kao Caspase-mediated Specific Cleavage of Human Histone Deacetylase 4 J. Biol. Chem., August 13, 2004; 279(33): 34537 - 34546. [Abstract] [Full Text] [PDF]

				K. Wu, S.-W. Jiang, and F. J. Couch p53 Mediates Repression of the BRCA2 Promoter and Down-regulation of BRCA2 mRNA and Protein Levels in Response to DNA Damage J. Biol. Chem., April 25, 2003; 278(18): 15652 - 15660. [Abstract] [Full Text] [PDF]

				M. H. Wu and B. Y. M. Yung UV Stimulation of Nucleophosmin/B23 Expression Is an Immediate-early Gene Response Induced by Damaged DNA J. Biol. Chem., December 6, 2002; 277(50): 48234 - 48240. [Abstract] [Full Text] [PDF]