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 Filippov, V. Articles by Duerksen-Hughes, P. J. Search for Related Content PubMed PubMed Citation Articles by Filippov, V. Articles by Duerksen-Hughes, P. J.

The Early Response to DNA Damage Can Lead to Activation of Alternative Splicing Activity Resulting in CD44 Splice Pattern Changes

Department of Biochemistry and Microbiology, Loma Linda University School of Medicine, Loma Linda, California

Requests for reprints: Penelope J. Duerksen-Hughes, Department of Biochemistry and Microbiology, 121 Mortensen Hall, Loma Linda University School of Medicine, Loma Linda, CA 92354. Phone: 909-558-4300, ext. 81361; Fax: 909-558-0177; E-mail: pdhughes{at}llu.edu.

Expression of the human papillomavirus 16 E6 oncogene interferes with several vital cellular processes, including the p53-dependent response to DNA damage. To assess the influence of E6 on the early response to DNA damage, we analyzed gene expression following mitomycin C–induced genotoxic stress in human E6–expressing U2OS cells (U2OSE64b) as well as in p53-expressing control cells (U2OSE6AS) by comparative global expression profiling. As expected, genes involved in p53-dependent pathways were activated in p53-expressing cells. In the U2OSE64b cells, however, a largely nonoverlapping group of genes was identified, including two splicing factors of the SR family. Immunoblot analysis revealed increased expression of several SR proteins during the early response to DNA damage, which was accompanied by activation of alternative splicing activity. Disruption of splicing activity by treatment with small interfering RNA directed against splicing factor SRp55 resulted in the increased viability of p53-deficient cells following DNA damage. To determine whether the transient activation of splicing activity was due to E6-mediated degradation of p53, or was due to some other activity of E6, we compared the early response of the p53 wild-type and p53–/– isogenic HCT116 cell lines, and found that the increase in splicing activity was observed only in the absence of p53. Finally, both the U2OSE64b and the p53–/– cells showed altered splicing patterns for the CD44 receptor. Together, these data show that cells lacking p53 can activate alternative splicing following DNA damage. [Cancer Res 2007;67(16):7621–30]

This article has been cited by other articles:

				K. Takeo, T. Kawai, K. Nishida, K. Masuda, S. Teshima-Kondo, T. Tanahashi, and K. Rokutan Oxidative stress-induced alternative splicing of transformer 2{beta} (SFRS10) and CD44 pre-mRNAs in gastric epithelial cells Am J Physiol Cell Physiol, August 1, 2009; 297(2): C330 - C338. [Abstract] [Full Text] [PDF]

				J. R. LOPEZ-EGIDO, Y. WANG, M. GRONBERG, P. GRIMFJARD, S. WANG, P. STALBERG, and B. SKOGSEID Differentially Regulated Genes in MEN1-transfected BON Cells Using RT-differential Display and Oligonucleotide Microarrays Anticancer Res, June 1, 2009; 29(6): 1859 - 1866. [Abstract] [Full Text] [PDF]