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Cell Rep. 2012 Feb 23;1(2):110-7.

Oncogenic splicing factor SRSF1 is a critical transcriptional target of MYC.

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1
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

Abstract

The SR protein splicing factor SRSF1 is a potent proto-oncogene that is frequently upregulated in cancer. Here, we show that SRSF1 is a direct target of the transcription factor oncoprotein MYC. These two oncogenes are significantly coexpressed in lung carcinomas, and MYC knockdown downregulates SRSF1 expression in lung-cancer cell lines. MYC directly activates transcription of SRSF1 through two noncanonical E-boxes in its promoter. The resulting increase in SRSF1 protein is sufficient to modulate alternative splicing of a subset of transcripts. In particular, MYC induction leads to SRSF1-mediated alternative splicing of the signaling kinase MKNK2 and the transcription factor TEAD1. SRSF1 knockdown reduces MYC's oncogenic activity, decreasing proliferation and anchorage-independent growth. These results suggest a mechanism for SRSF1 upregulation in tumors with elevated MYC and identify SRSF1 as a critical MYC target that contributes to its oncogenic potential by enabling MYC to regulate the expression of specific protein isoforms through alternative splicing.

PMID:
22545246
PMCID:
PMC3334311
DOI:
10.1016/j.celrep.2011.12.001
[Indexed for MEDLINE]
Free PMC Article
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