Your browser version may not work well with NCBI's Web applications. More information here...
1: Nat Struct Mol Biol. 2007 Mar;14(3):185-93. Epub 2007 Feb 18.
Related Articles, Links
Click here to read Click here to read
Comment in:
The gene encoding the splicing factor SF2/ASF is a proto-oncogene.

Karni R, de Stanchina E, Lowe SW, Sinha R, Mu D, Krainer AR.

Cold Spring Harbor Laboratory, PO Box 100, Cold Spring Harbor, New York 11724, USA.

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.

Publication Types:
PMID: 17310252 [PubMed - indexed for MEDLINE]