Unknown

Dataset Information

0

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


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.

SUBMITTER: Karni R 

PROVIDER: S-EPMC4595851 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Karni Rotem R   de Stanchina Elisa E   Lowe Scott W SW   Sinha Rahul R   Mu David D   Krainer Adrian R AR  

Nature structural & molecular biology 20070218 3


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  ...[more]

Similar Datasets

| S-EPMC2563124 | biostudies-literature
| S-EPMC1635291 | biostudies-literature
| S-EPMC5548014 | biostudies-literature
| S-EPMC3395997 | biostudies-literature
| S-EPMC2876523 | biostudies-literature
| S-EPMC3031499 | biostudies-literature
| S-EPMC2965252 | biostudies-literature
| S-EPMC1283963 | biostudies-literature
| S-EPMC2998123 | biostudies-literature
| S-EPMC41207 | biostudies-other