SUMOYLATION ATTENUATES C-MAF-DEPENDENT IL-4 EXPRESSION
Resource
EUROPEAN JOURNAL OF IMMUNOLOGY, 40(4), 1174-1184
Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Journal Volume
40
Journal Issue
4
Pages
1174-1184
Date Issued
2010-01
Date
2010-01
Author(s)
LIN, BO-SHIOU
TSAI, PEI-YUN
HSIEH, WAN-YUN
TSAO, HSIAO-WEI
LIU, MENG-WEI
WANG, LI-FANG
MIAW, SHI-CHUEN
Abstract
The function of transcription factors can be critically regulated by SUMOylation. c-Maf, the cellular counterpart of v-maf oncogene, is a potent transactivator of the IL-4 gene in Th2 cells. We found in a yeast two-hybrid screen that c- Maf can interact with Ubc9 and PIAS1, two key enzymes of the SUMOylation pathway. In this study, we report that c-Maf co-localized with these two SUMO (small ubiquitin-like modifier) ligases in the nucleus and that c-Maf can be SUMOylated in vitro and also in primary Th2 cells. We also demonstrated that lysine-33 is the dominant, if not the only , SUMO acceptor site of c-Maf. SUMOylation of c-Maf attenuated its transcriptional activity. Reciprocally, a SUMOylation resistant c-Maf was more potent than WT-c-Maf in driving IL-4 production in c-Maf-deficient Th2 cells. Furthermore, we showed that ablation of the SUMO site did not alter the subcellular localization or the stability of c -Maf protein but instead enhanced its recruitment to the I14 -promoter. We conclude that SUMOylation at lysine-33 is a functionally critical post-translational modification event of c-Maf in Th cells.
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