Bi H, Li S, Wang M, Jia Z, Chang AK, Pang P, Wu H

G-protein pathway suppressor 2 (GPS2) is a human suppressor of G protein-activated-MAPK signaling. It is involved in many physiological processes, including DNA repair, cell proliferation, apoptosis, and brain development. In this study, we showed that GPS2 could be modified by the small ubiquitin-like modifier (SUMO), SUMO-1, but not SUMO-2 or ...

Read More

-3. Two SUMOylation sites (K45 and K71) were identified in the N-terminal coiled-coil domain of GPS2. Substitution of K45 with arginine reduced SUMOylation, whereas substitution of K71 or both K45 and K71 with arginine abolished SUMOylation, with more of the double mutant GPS2 appeared in the cytosol than in the nucleus compared to wild-type and the two single mutant GPS2. SUMOylation stabilized GPS2 protein through promoting its interaction with TBL1 and reducing its ubiquitination. SUMOylation also enhanced the ability of GPS2 to suppress transcription and promoted its ability to inhibit ERα-mediated transcription by increasing its association with SMRT as demonstrated in MCF-7 cells and T47D cells. Moreover, SUMOylation of GPS2 also repressed the proliferation of MCF-7 and T47D cells. These findings suggested that posttranslational modification of GPS2 by SUMOylation may serve as a key factor that regulates the function of GPS2 in vivo.

Date: Jun. 18, 2014

View in: Pubmed Google Scholar

165554