Regulation of Akt activity by SUMO conjugation

GUILLERMO RISSO; FEDERICO PELISCH; BERTA POZZI; MATÍAS BLAUSTEIN; ALEJANDRO COLMAN-LERNER; ANABELLA SREBROW

Puerto Madryn, Argentina

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2010

A cell generates complex responses upon a variety of stimuli that it receives within a multicellular organism. Our lab studies the molecular mechanisms by which different extracellular cues activate signaling pathways that control splicing factor activity at different steps of gene expression regulation. Based on our previous results demonstrating that: i) Pi3K/Akt pathway regulates alternative splicing; ii) Akt phosphorylates SR proteins, in particular SF2/ASF; and iii) SF2/ASF regulates SUMOylation, we proposed to explore a possible regulatory feedback loop among the components of the Pi3K/Akt/SR protein axis.We found that Akt1 and 2 are SUMOylation targets, as demonstrated by purification of SUMOylated proteins from His-SUMO overexpressing cells by Ni2+ affinity chromatography. We evaluated the effect of over-expressing different SUMO E3 ligases on Akt SUMOylation. Interestingly, SF2/ASF is capable of regulating Akt SUMOylation and phosphorylation levels. We are further dissecting the mechanism of Akt SUMOylation, its cross-talk with other Akt post-translational modifications, as well as the consequences on this kinase activity. Akt pathways are involved in many cellular functions and their dis-regulation associates with cancer, thus the understanding of Akt activity regulation is not only relevant for cell biology but may also help designing antitumoral therapeutic strategies.