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Cell Death Differ. 2008 Dec;15(12):1815-23. doi: 10.1038/cdd.2008.135. Epub 2008 Sep 19.

E2F1 controls alternative splicing pattern of genes involved in apoptosis through upregulation of the splicing factor SC35.

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1
INSERM, U823, Equipe 2 Bases Mol├ęculaires de la Progression des Cancers du Poumon, Grenoble, 38042, France.

Abstract

The transcription factor E2F1 has a key function during S phase progression and apoptosis. It has been well-demonstrated that the apoptotic function of E2F1 involves its ability to transactivate pro-apoptotic target genes. Alternative splicing of pre-mRNAs also has an important function in the regulation of apoptosis. In this study, we identify the splicing factor SC35, a member of the Ser-Rich Arg (SR) proteins family, as a new transcriptional target of E2F1. We demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of various apoptotic genes such as c-flip, caspases-8 and -9 and Bcl-x, towards the expression of pro-apoptotic splice variants. Finally, we provide evidence that E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is required for apoptosis in response to these drugs. Taken together, these results demonstrate that E2F1 controls pre-mRNA processing events to induce apoptosis and identify the SC35 SR protein as a key direct E2F1-target in this setting.

PMID:
18806759
DOI:
10.1038/cdd.2008.135
[Indexed for MEDLINE]
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