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 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.
Chou
Chih-Chine
CC
Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, the.
Chang
Chingwen
C
Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, the.
Liu
Jyung-Hurng
JH
Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan, and the.
Chen
Liang-Fu
LF
Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, the.
Hsiao
Chwan-Deng
CD
Institute of Molecular Biology, Academia Sinica, Nankang, Taipei 115, Taiwan, and the.
Chen
Hungwen
H
Graduate Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan, the; Institute of Biological Chemistry, Academia Sinica, Nankang, Taipei 115, Taiwan. Electronic address: hwchen@gate.sinica.edu.tw.
D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins; D015686:Gene Products, env / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000235:genetics; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C491089:GCM1 protein, human; D015686:Gene Products, env; D009687:Nuclear Proteins; D011257:Pregnancy Proteins; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; C405335:syncytin; D004247:DNA