EWS.Fli-1 fusion protein interacts with hyperphosphorylated RNA polymerase II and interferes with serine-arginine protein-mediated RNA splicing.
J Biol Chem
; 275(48): 37612-8, 2000 Dec 01.
Article
em En
| MEDLINE
| ID: mdl-10982800
ABSTRACT
Ewing's sarcoma displays a characteristic chromosomal translocation that results in fusion of the N-terminal domain of the Ewing's sarcoma protein (EWS) to the C-terminal DNA-binding domain of the ETS family transcription factor Fli-1 (Friend leukemia integration-1). EWS possesses structural motifs suggesting a role in transactivation as well as RNA binding. We demonstrate that wild-type EWS protein functions as an adapter molecule coupling transcription to RNA splicing by binding to hyperphosphorylated RNA polymerase II through the N-terminal domain of EWS and recruiting serine-arginine (SR) splicing factors through the C-terminal domain of EWS. The oncogenic EWS.Fli-1 fusion protein retains the ability to bind to hyperphosphorylated RNA polymerase II but lacks the ability to recruit SR proteins because of replacement of the C-terminal domain of EWS by Fli-1. In an in vivo splicing assay, the EWS.Fli-1 fusion protein inhibits SR protein-mediated E1A pre-mRNA splicing in a dominant-negative manner. These results indicate that EWS.Fli-1 interferes with the normal function of EWS and implicate uncoupling of gene transcription from RNA splicing in the pathogenesis of Ewing's sarcoma.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arginina
/
Serina
/
Fatores de Transcrição
/
RNA Polimerase II
/
Proteínas de Fusão Oncogênica
/
Splicing de RNA
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Biol Chem
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos