Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC

Das, S., Anczuków, O., Akerman, M., Krainer, A. R (2012) Oncogenic Splicing Factor SRSF1 Is a Critical Transcriptional Target of MYC. Cell Reports, 1 (2). pp. 110-117. ISSN 2211-1247

Abstract

Summary 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.

Item Type:	Paper
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > Myc bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:	Akerman, Martin Das, Shipra Krainer, Adrian R. Anczukow, Olga
Communities:	CSHL Post Doctoral Fellows CSHL labs > Krainer lab
Depositing User:	Matt Covey
Date:	2012
Date Deposited:	31 Jan 2013 20:33
Last Modified:	19 Jul 2021 20:24
PMCID:	PMC3334311
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/26926

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