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

FEDERICO PELISCH; ANABELLA SREBROW

Riva del Garda, Italia

Conferencia; RUBICON and EMBO Conference: Ubiquitin and Ubiquitin-like Modifiers in Health and Disease; 2009

RUBICON and EMBO

<!-- /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman"; mso-bidi-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:72.0pt 90.0pt 72.0pt 90.0pt; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --> 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 its components, mechanisms and consequences. We found that the serine/arginine-rich protein SF2/ASF, a factor involved in splicing regulation and other steps of RNA metabolism, is a regulator of the sumoylation pathway. Its over-expression stimulates while its knockdown inhibits SUMO conjugation. SF2/ASF interacts with the sumo conjugating enzyme Ubc9 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 not only necessary but also 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.