The Serine-Arginine rich protein SF2/ASF regulates protein SUMOylation

ANABELLA SREBROW; FEDERICO PELISCH

San Miguel de TUCUMAN

Congreso; XLV Congreso Anual de la Sociedad Argentina de Investigacion en Bioquímicas y Biología Molecular (SAIB; 2009

SAIB

Post-translational protein modification by SUMO is involved in diverse biological functions such as transcription regulation, subcellular partitioning, stress response, DNA damage repair and chromatin remodeling. SUMO conjugation to target proteins proceeds by an enzymatic pathway involving an E1 activating enzyme, an E2 conjugating enzyme and E3 ligases. Ser/Arg-rich (SR) proteins, initially described as splicing regulators, also play important roles in other steps along mRNA metabolism. Considering that the SUMO E3 ligase PIAS1 localizes to nuclear speckles, resembles scaffold-attachment factors shown to interact with RNA polimerase II and SR proteins, and is part of the human spliceosome, we decided to investigate a possible involvement of SR proteins in the SUMOylation process. We found that the SR protein SF2/ASF is a regulator of the SUMO pathway, in vitro and in vivo. Its over-expression stimulates while its knockdown inhibits SUMO conjugation. SF2/ASF interacts with the E2 enzyme and enhances the SUMOylation of specific target proteins, behaving as an E3 ligase. It also interacts with the SUMO E3 ligase PIAS1, regulating its activity. The RNA recognition motif 2 of SF2/ASF is necessary and sufficient for SUMOylation enhancement. These results add a further level of regulation to the SUMOylation pathway and also a new role for the multifunctional SR protein SF2/ASF.