Small Ubiquitin-like Modifier Modification Regulates the DNA Binding Activity of Glial Cell Missing Drosophila Homolog a

Glial cell missing Drosophila homolog a (GCMa) is an essential transcription factor for placental development, which controls the differentiation of the syncytiotrophoblast layer. Although the activity of GCMa can be post-translationally regulated by protein phosphorylation, ubiquitination, and acet...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2007-09, Vol.282 (37), p.27239-27249
Main Authors: Chou, Chih-Chine, Chang, Chingwen, Liu, Jyung-Hurng, Chen, Liang-Fu, Hsiao, Chwan-Deng, Chen, Hungwen
Format: Article
Language:English
Subjects:
DNA - metabolism
DNA-Binding Proteins
Drosophila
Gene Products, env - genetics
Humans
Nuclear Proteins - chemistry
Nuclear Proteins - metabolism
Pregnancy Proteins - genetics
Small Ubiquitin-Related Modifier Proteins - chemistry
Small Ubiquitin-Related Modifier Proteins - physiology
Transcription Factors - chemistry
Transcription Factors - metabolism
Transcription, Genetic
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Glial cell missing Drosophila homolog a (GCMa) is an essential transcription factor for placental development, which controls the differentiation of the syncytiotrophoblast layer. Although the activity of GCMa can be post-translationally regulated by protein phosphorylation, ubiquitination, and acetylation, it is unknown whether GCMa activity can be regulated by sumoylation. In this report, we investigated the role of sumoylation in the regulation of GCMa activity. We demonstrated that Ubc9, the E2 component of the sumoylation machinery, specifically interacts with the N-terminal domain of GCMa and promotes GCMa sumoylation on lysine 156. Moreover, GCMa-mediated transcriptional activation was repressed by sumoylation but was enhanced in the presence of the SUMO-specific protease, SENP1. The repressive effect of sumoylation on GCMa transcriptional activity was attributed to decreased DNA binding activity of GCMa. Furthermore, structural analysis revealed a steric clash between the SUMO1 moiety of sumoylated GCMa and the DNA-binding surfaces of GCMa, which may destabilize the interaction between GCMa and its cognate DNA sequence. Our study demonstrates that GCMa is a new sumoylation substrate and its activity is down-regulated by sumoylation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M700351200