The polycomb group protein Pc2 has been identified as a new SUMO E3 that recruits the transcriptional corepressor CtBP and the E2 enzyme Ubc9 to PcG bodies, thereby enhancing CtBP sumoylation.
Polycomb group (PcG) proteins stably repress gene expression and form complexes with each other. PcG complexes, in turn, form discrete nuclear foci, known as PcG bodies, into which other transcriptional regulators might be recruited. As reported in Cell, the PcG protein Pc2 has now been identified as a new SUMO E3 that recruits the transcriptional corepressor CtBP and the E2 (conjugating) enzyme Ubc9 to PcG bodies, thereby enhancing CtBP sumoylation.
The single sumoylation motif in CtBP hinted to David Wotton's group that CtBP could be sumoylated. In vitro, CtBP sumoylation minimally required recombinant E1 (an activating enzyme), Ubc9 and SUMO-1. In vivo, CtBP immunoprecipitated from HeLa cells was detected with an anti-SUMO-1-specific antibody. Lysine 428 of CtBP was identified as the principal site for SUMO conjugation, and the surrounding motif was important for efficient sumoylation.
CtBP can be nuclear and cytoplasmic but, in the presence of recombinant Pc2, much of it colocalized with Pc2 in nuclear foci, where it was found to be sumoylated. Pc2 itself was also sumoylated, so could Pc2 affect SUMO localization? Co-expressing Pc2 caused SUMO-1 and Ubc9 to move to nuclear foci. Pc2 colocalized there, too, suggesting that these foci were probably PcG bodies.
As Pc2 co-expression caused the recruitment of a SUMO substrate (CtBP) and an E2 enzyme (Ubc9) to the same compartment, the authors tested Pc2's ability to enhance CtBP sumoylation. In cell-based and in vitro sumoylation assays, recombinant Pc2 increased the amount of sumoylated CtBP.
So PcG bodies might function as centres of sumoylation in the nucleus. The authors speculate that "...PcG complexes may exert their effects on transcription in part by mediating the sumoylation of specific target proteins" and that CtBP, which might bridge interactions between transcriptional regulators, along with Pc2, could be "...part of the PcG sumoylation machine...".
Katrin Bussell
References
Kagey, M. H., Melhuish, T. A. & Wotton, D. The Polycomb protein Pc2 is a SUMO E3. Cell113, 127–137 (2003) | PubMed |
Muller, S. et al. SUMO, ubiquitin's mysterious cousin. Nature Rev. Mol. Cell Biol.2, 202–210 (2001) | Article | PubMed |
