Mel-18 interacts with RanGAP1 and inhibits its sumoylation

• Published in: Biochemical and biophysical research communications 2008-10, Vol.375 (2), p.252-255
• Main Authors: Zhang, Jie, Sarge, Kevin D.
• Format: Article
• Language: English
• Subjects: Cell Line; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; GTPase-Activating Proteins - metabolism; Humans; Mel-18; Mitosis; Polycomb; Polycomb Repressive Complex 1; RanGAP1; Repressor Proteins - genetics; Repressor Proteins - metabolism; RING Finger Domains - genetics; Small Ubiquitin-Related Modifier Proteins - antagonists & inhibitors; SUMO; SUMO-1; Ubiquitin-Conjugating Enzymes - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.08.012

Our previous results showed that the polycomb protein mel-18 binds to a protein called HSF2 and inhibits HSF2 sumoylation, thereby functioning as an anti-SUMO E3 factor. This study also suggested that mel-18 regulates the sumoylation of other cellular proteins, but the identities of these other proteins were unknown. Here we show that mel-18 interacts with the RanGAP1 protein and inhibits its sumoylation, and that these activities do not require the RING domain of mel-18. The results also show that RanGAP1 sumoylation is decreased during mitosis, and that this is associated with increased interaction between RanGAP1 and mel-18 during this stage of the cell cycle. Intriguingly, this regulatory relationship is the opposite of that found for mel-18 and HSF2, in which the interaction between these two proteins decreases during mitosis, resulting in elevated HSF2 sumoylation. The results of this study strengthen the conclusion that mel-18 functions as an anti-SUMO E3 factor, and extend its targets to include regulation of the sumoylation of the important cellular protein RanGAP1.