The gene encoding the splicing factor SF2/ASF is a proto-oncogene

Karni, R., de Stanchina, E., Lowe, S. W., Sinha, R., Mu, D., Krainer, A. R. (March 2007) The gene encoding the splicing factor SF2/ASF is a proto-oncogene. Nat Struct Mol Biol, 14 (3). pp. 185-93. ISSN 1545-9993 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/17310252
DOI: 10.1038/nsmb1209

Abstract

Alternative splicing modulates the expression of many oncogene and tumor-suppressor isoforms. We have tested whether some alternative splicing factors are involved in cancer. We found that the splicing factor SF2/ASF is upregulated in various human tumors, in part due to amplification of its gene, SFRS1. Moreover, slight overexpression of SF2/ASF is sufficient to transform immortal rodent fibroblasts, which form sarcomas in nude mice. We further show that SF2/ASF controls alternative splicing of the tumor suppressor BIN1 and the kinases MNK2 and S6K1. The resulting BIN1 isoforms lack tumor-suppressor activity; an isoform of MNK2 promotes MAP kinase-independent eIF4E phosphorylation; and an unusual oncogenic isoform of S6K1 recapitulates the transforming activity of SF2/ASF. Knockdown of either SF2/ASF or isoform-2 of S6K1 is sufficient to reverse transformation caused by the overexpression of SF2/ASF in vitro and in vivo. Thus, SF2/ASF can act as an oncoprotein and is a potential target for cancer therapy.

Item Type: Paper
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > splicing factor
CSHL Authors:
Communities: CSHL labs > Krainer lab
CSHL labs > Lowe lab
Depositing User: CSHL Librarian
Date: March 2007
Date Deposited: 11 Nov 2011 16:41
Last Modified: 09 Apr 2014 14:31
Related URLs:
URI: http://repository.cshl.edu/id/eprint/23059

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