CONICET | Buscador de Institutos y Recursos Humanos

Protein modification by conjugation of small ubiquitin-related modifiers (SUMO1, 2 and 3) is involved in diverse biological functions, namely transcription regulation, sub-cellular partitioning, stress response, DNA damage repair and chromatin remodeling. Since its discovery more than a decade ago, there has been an enormous advance in the knowledge of many aspects of the sumoylation pathway. However, there is a great void regarding components, mechanisms and consequences. We found that the serine/arginine-rich protein SF2/ASF functions at two levels in the sumoylation cascade. It interacts with ubc9 and enhances the sumoylation of specific target proteins, behaving as an E3 ligase and also interacts with the SUMO E3 ligase PIAS1 and regulates its activity. SF2/ASF enhances overall protein sumoylation and, furthermore, the stimulatory effect of PIAS1 on sumoylation depends on SF2/ASF, showing that these two proteins cooperate to regulate sumoylation. These results not only add a further level of regulation to the sumoylation pathway but also a new role for the multifunctional SR protein SF2/ASF.