| Summary: | 碩士 === 國立臺灣大學 === 生化科學研究所 === 94 === Human placental transcription factor GCMa (hGCMa) is a member of the GCM gene family with a characteristic zinc-containing DNA-binding domain called GCM domain. hGCMa regulates expression of the fusogenic protein, syncytin, in order to facilitate the fusion of cytotrophoblasts into syncytiotrophoblasts on placental villi. Syncytiotrophoblast mediates fetal-maternal exchange of gas and nutrients.
Previous studies indicated that hGCMa activity can be regulated by post-translational modifications such as ubiquitination and acetylation. In this study, we further investigated whether sumoylation, another post-translational modification, can regulate hGCMa activity. We demonstrated that hGCMa specifically interacts with the SUMO E2 protein, Ubc9, via the N-terminal GCM domain of hGCMa. In addition, Ubc9 promoted the conjugation between hGCMa and SUMO-1 in vivo and in vitro. The lysine156 residue in hGCMa was identified as the major sumoylation site. Moreover, coexpression of the SUMO E3 protein, PIAS2β, and Ubc9 further promoted the degree of hGCMa sumoylation. Examining the role of SUMO-1 in the regulation of hGCMa activity revealed that SUMO-1 modification decreases the transcriptional activity of hGCMa. Conversely, coexpression of SENP1, a desumolyation enzyme, indeed increased hGCMa-mediated transcriptional activation.
Overall, our results support that hGCMa can undergo sumoylation, which further suppresses hGCMa transcriptional activity. To our knowledge, hGCMa is the first identified GCM member that can be post-translationally modified by SUMO-1. Our results further our understanding on how hGCMa activity is regulated, which may also help to understand the regulation of trophoblastic fusion.
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