This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Revil, T.
Right arrow Articles by Chabot, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Revil, T.
Right arrow Articles by Chabot, B.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2007, p. 8431-8441, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.00565-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Protein Kinase C-Dependent Control of Bcl-x Alternative Splicing{triangledown}

Timothée Revil, Johanne Toutant, Lulzim Shkreta, Daniel Garneau, Philippe Cloutier, and Benoit Chabot*

RNA/RNP Group, Département de Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4

Received 30 March 2007/ Returned for modification 7 May 2007/ Accepted 19 September 2007

The alternative splicing of Bcl-x generates the proapoptotic Bcl-xS protein and the antiapoptotic isoform Bcl-xL. Bcl-x splicing is coupled to signal transduction, since ceramide, hormones, and growth factors alter the ratio of the Bcl-x isoforms in different cell lines. Here we report that the protein kinase C (PKC) inhibitor and apoptotic inducer staurosporine switches the production of Bcl-x towards the xS mRNA isoform in 293 cells. The increase in Bcl-xS elicited by staurosporine likely involves signaling events that affect splicing decisions, because it requires active transcription and no new protein synthesis and is independent of caspase activation. Moreover, the increase in Bcl-xS is reproduced with more specific inhibitors of PKC. Alternative splicing of the receptor tyrosine kinase gene Axl is similarly affected by staurosporine in 293 cells. In contrast to the case for 293 cells, PKC inhibitors do not influence the alternative splicing of Bcl-x and Axl in cancer cell lines, suggesting that these cells have sustained alterations that uncouple splicing decisions from PKC-dependent signaling. Using minigenes, we show that an exonic region located upstream of the Bcl-xS 5' splice site is important to mediate the staurosporine shift in Bcl-x splicing. When transplanted to other alternative splicing units, portions of this region confer splicing modulation and responsiveness to staurosporine, suggesting the existence of factors that couple splicing decisions with PKC signaling.

* Corresponding author. Mailing address: RNA/RNP Group, Département de Microbiologie et d'Infectiologie, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4. Phone: (819) 564-5295. Fax: (819) 564-5392. E-mail: Benoit.Chabot{at}USherbrooke.ca

{triangledown} Published ahead of print on 8 October 2007.

Molecular and Cellular Biology, December 2007, p. 8431-8441, Vol. 27, No. 24
0270-7306/07/$08.00+0     doi:10.1128/MCB.00565-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Venables, J. P., Koh, C.-S., Froehlich, U., Lapointe, E., Couture, S., Inkel, L., Bramard, A., Paquet, E. R., Watier, V., Durand, M., Lucier, J.-F., Gervais-Bird, J., Tremblay, K., Prinos, P., Klinck, R., Elela, S. A., Chabot, B. (2008). Multiple and Specific mRNA Processing Targets for the Major Human hnRNP Proteins. Mol. Cell. Biol. 28: 6033-6043 [Abstract] [Full Text]  
  • Zhou, A., Ou, A. C., Cho, A., Benz, E. J. Jr., Huang, S.-C. (2008). Novel Splicing Factor RBM25 Modulates Bcl-x Pre-mRNA 5' Splice Site Selection. Mol. Cell. Biol. 28: 5924-5936 [Abstract] [Full Text]  
  • Cloutier, P., Toutant, J., Shkreta, L., Goekjian, S., Revil, T., Chabot, B. (2008). Antagonistic Effects of the SRp30c Protein and Cryptic 5 ' Splice Sites on the Alternative Splicing of the Apoptotic Regulator Bcl-x. J. Biol. Chem. 283: 21315-21324 [Abstract] [Full Text]  
  • Hai, Y., Cao, W., Liu, G., Hong, S.-P., Elela, S. A., Klinck, R., Chu, J., Xie, J. (2008). A G-tract element in apoptotic agents-induced alternative splicing. Nucleic Acids Res 36: 3320-3331 [Abstract] [Full Text]  
  • Shkreta, L., Froehlich, U., Paquet, E. R., Toutant, J., Elela, S. A., Chabot, B. (2008). Anticancer drugs affect the alternative splicing of Bcl-x and other human apoptotic genes. Molecular Cancer Therapeutics 7: 1398-1409 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»