The SR protein SRSF1 at different levels of the SUMO conjugation pathway

RISSO, GUILLERMO; PELISCH FEDERICO; POZZI, BERTA; SREBROW ANABELLA

IGUAZU

Congreso; Gene Expression and RNA Processing; 2011

ICGEB, ANPCyT y CONICET

FROM THE ROLE OF SRSF1 AS A COMPONENT OF THE SUMO CONJUGATION PATHWAY TO THE INVOLVEMENT OF AKT SUMOYLATION IN SPLICING REGULATION G. Risso, F. Pelisch, B. Pozzi and A. Srebrow Laboratorio de Fisiología y Biología Molecular, IFIBYNE-CONICET, FCEyN-UBA, Buenos Aires, Argentina E-mail: guillermorisso@fbmc.fcen.uba.ar 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 SRSF1 (previously known as SF2/ASF); and iii) SRSF1 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 Akt2 are SUMOylation targets, as demonstrated by purification of SUMOylated proteins from His-SUMO over-expressing cells by Ni2+ affinity chromatography. When evaluating the effect of over-expressing different SUMO E3 ligases on Akt SUMOylation, we observed that SRSF1 is capable of regulating Akt SUMOylation levels. Furthermore, we found that SRSF1 is also a SUMOylation target and, by using SRSF1 deletion mutants we mapped the SUMO conjugation residue to the RRM2 domain. We are currently exploring the consequences of the previously unknown post-translational modification of SRSF1 and Akt by SUMO conjugation on the different activities of these two proteins, focusing on alternative splicing regulation.