INVESTIGADORES
BLAUSTEIN KAPPELMACHER Matias
congresos y reuniones científicas
Título:
Regulation of alternative splicing in the mammary gland differentiation
Autor/es:
FEDERICO PELISCH; MATÍAS BLAUSTEIN; LEANDRO QUADRANA; ANABELLA SREBROW
Lugar:
Pinamar, Argentina
Reunión:
Congreso; Reunión Anual de la Sociedad Argentina de Investigaciones Bioquímicas - SAIB; 2005
Resumen:
Alternative splicing generates distinct proteins from a single gene. The fibronectin (FN) gene provides a paradigmatic model for studying alternative splicing regulation. We have previously shown that growth factors (GF) secreted by mesenchymal cells up-regulate FN EDI and IIICS exon inclusion in mammary epithelial cells via PI 3-kinase and, on the contrary, a basement membrane-like extracellular matrix (BM) down-modulates the inclusion of these alternative regions. Using siRNAs and pharmacological inhibitors we showed that this effect is entirely dependent on the activation of JNK. Furthermore, the BM inhibits the effects of GF on alternative splicing, consistent with the opposite roles reported for PI 3-kinase and JNK. Over-expression of a constitutively active form of AKT reproduces the effect of GF on alternative splicing, and this effect is completely inhibited by the over-expression of JNK. On the other hand, treatment with BM triggers ERK dephosphorylation. We are currently investigating its involvement in FN splicing regulation. These results strengthen our understanding of how extracellular stimuli are converted into changes in splicing patterns, highlighting the fact that the splicing pattern of a single transcript is the read out of an intricate network of different signaling pathways.