Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/1946
Título: Phosphorylation of SRSF1 by SRPK1 regulates alternative splicing of tumor-related Rac1b
Autor: Gonçalves, Vânia
Matos, Paulo
Neves-Costa, Ana
Moyer, M.P.
Ferreira-Moita, Luís
Gama-Carvalho, Margarida
Jordan, Peter
Palavras-chave: Vias de Transdução de Sinal e Patologias Associadas
Rac1b
Alternative Splicing
Colon Cancer
SRPK1
Data: 6-Dez-2013
Editora: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Resumo: The pre-messenger RNA of the majority of human genes can generate various transcripts through alternative splicing, and different tissues or disease states show specific patterns of splicing variants. These patterns depend on the relative concentrations of the splicing factors present in the cell nucleus, either as a consequence of their expression levels or of post-translational modifications such as protein phosphorylation, which are determined by signal transduction pathways. Here we analyzed the contribution of protein kinases to the regulation of alternative splicing variant Rac1b that is overexpressed in certain tumor types. In colorectal cells we found that depletion of AKT2, AKT3, GSK3β and SRPK1 significantly decreased endogenous Rac1b levels. Whereas knockdown of AKT2 and AKT3 affected only Rac1b protein levels suggesting a post-splicing effect, the depletion of GSK3β or SRPK1 decreased Rac1b alternative splicing, an effect mediated through changes in splicing factor SRSF1. In particular, the knockdown of SRPK1 or inhibition of its catalytic activity reduced phosphorylation and subsequent translocation of SRSF1 to the nucleus, limiting its availability to promote the inclusion of alternative exon 3b into the Rac1 pre-mRNA. Altogether, the data identify SRSF1 as a prime regulator of Rac1b expression in colorectal cells and provide further mechanistic insights into how the regulation of alternative splicing events by protein kinases can contribute to sustain tumor cell survival.
URI: http://hdl.handle.net/10400.18/1946
Aparece nas colecções:DGH - Posters/abstracts em congressos nacionais

Ficheiros deste registo:
Ficheiro Descrição TamanhoFormato 
posterRac1b Vania_SINAL2013.pdf4,67 MBAdobe PDFVer/Abrir    Acesso Restrito. Solicitar cópia ao autor!


FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpace
Formato BibTex MendeleyEndnote Degois 

Todos os registos no repositório estão protegidos por leis de copyright, com todos os direitos reservados.