Ets-1 p27: A novel Ets-1 isoform with dominant-negative effects on the transcriptional properties and the subcellular localization of Ets-1 p51
Data(s) |
01/05/2009
|
---|---|
Resumo |
The transcription factor Ets-1 is implicated in various physiological processes and invasive pathologies. We identified a novel variant of ets-1, ets-1Delta(III-VI), resulting from the alternative splicing of exons III to VI. This variant encodes a 27 kDa isoform, named Ets-1 p27. Ets-1 p27 lacks the threonine-38 residue, the Pointed domain and the transactivation domain, all of which are required for the transactivation of Ets-1 target genes. Both inhibitory domains surrounding the DNA-binding domain are conserved, suggesting that Ets-1 p27, like the full-length Ets-1 p51 isoform, is autoinhibited for DNA binding. We showed that Ets-1 p27 binds DNA in the same way as Ets-1 p51 does and that it acts both at a transcriptional and a subcellular localization level, thereby constituting a dual-acting dominant negative of Ets-1 p51. Ets-1 p27 blocks Ets-1 p51-mediated transactivation of target genes and induces the translocation of Ets-1 p51 from the nucleus to the cytoplasm. Furthermore, Ets-1 p27 overexpression represses the tumor properties of MDA-MB-231 mammary carcinoma cells in correlation with the known implication of Ets-1 in various cellular mechanisms. Thus the dual-acting dominant-negative function of Ets-1 p27 gives to the Ets-1 p27/Ets-1 p51 ratio a determining effect on cell fate. SCOPUS: ar.j info:eu-repo/semantics/published |
Formato |
No full-text files |
Identificador |
uri/info:doi/10.1038/onc.2009.72 uri/info:pii/ONC200972 uri/info:pmid/19377509 http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/110436 |
Idioma(s) |
en |
Fonte |
Oncogene, 28 (20 |
Palavras-Chave | #Sciences bio-médicales et agricoles #Alternative splicing #Dominant-negative isoform #Ets-1 #Subcellular localization #Transcriptional regulation |
Tipo |
info:eu-repo/semantics/article info:ulb-repo/semantics/articlePeerReview info:ulb-repo/semantics/openurl/article |