Abstract
Protein modification by conjugation of small ubiquitin-related modifier (SUMO) is involved in diverse biological functions, such as transcription regulation, subcellular partitioning, stress response, DNA damage repair, and chromatin remodeling. Here, we show that the serine/arginine-rich protein SF2/ASF, a factor involved in splicing regulation and other RNA metabolism-related processes, is a regulator of the sumoylation pathway. The overexpression of this protein stimulates, but its knockdown inhibits SUMO conjugation. SF2/ASF interacts with Ubc9 and enhances sumoylation of specific substrates, sharing characteristics with already described SUMO E3 ligases. In addition, SF2/ASF interacts with the SUMO E3 ligase PIAS1 (protein inhibitor of activated STAT-1), regulating PIAS1-induced overall protein sumoylation. The RNA recognition motif 2 of SF2/ASF is necessary and sufficient for sumoylation enhancement. Moreover, SF2/ASF has a role in heat shock-induced sumoylation and promotes SUMO conjugation to RNA processing factors. These results add a component to the sumoylation pathway and a previously unexplored role for the multifunctional SR protein SF2/ASF.
Original language | English |
---|---|
Pages (from-to) | 16119-16124 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America |
Volume | 107 |
Issue number | 37 |
DOIs | |
Publication status | Published - 14 Sept 2010 |
Keywords
- posttranslational modification
- splicing factor
- RNA processing
- E3 ligase
- SPLICING FACTOR ASF/SF2
- HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEINS
- HUMAN TOPOISOMERASE-I
- MESSENGER-RNA
- SR PROTEINS
- SUMO MODIFICATION
- GENE-EXPRESSION
- E3 LIGASE
- TRANSLATION INITIATION
- PROTEOMIC ANALYSIS