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)
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: | https://repository.cshl.edu/id/eprint/23059 |
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