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

被引：728

作者：

Karni, Rotem ^{[1
]}

de Stanchina, Elisa ^{[1
]}

Lowe, Scott W. ^{[1
]}

Sinha, Rahul ^{[1
]}

Mu, David ^{[1
]}

Krainer, Adrian R. ^{[1
]}

机构：

[1] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2007年 / 14卷 / 03期

关键词：

D O I：

10.1038/nsmb1209

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：185 / 193

页数：9

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