Id1 enhances RING1b E3 ubiquitin ligase activity through the Mel-18/Bmi-1 polycomb group complex.
The helix-loop-helix inhibitor of differentiation and DNA binding (Id1) is well known as an oncogene in various tumors. Although it has been reported that Id1 promotes several oncogenic processes, it is still unclear whether Id1 functions through epigenetic transcriptional regulation. In this study, we examined the effect of Id1 on polycomb group (PcG) proteins, which are crucial epigenetic gene silencers, and found that Id1 regulated the expression of Mel-18 and Bmi-1, both of which belong to polycomb repressive complex 1. We also confirmed that Id1 induced Mel-18 downregulation, which was mediated by the Akt pathway, and consequently upregulated the transcription of its target gene, c-Myc. Using a promoter-reporter, we demonstrated that Id1 regulated Bmi-1 transcription through c-Myc binding to its E-box in the promoter. Finally, we examined the activity of E3 ligase RING1b, whose catalytic activity is increased by binding with the RING finger protein Bmi-1, and found that Id1 overexpression enhanced RING1b E3 ligase activity leading to accumulation of H2A ubiquitination and ubiquitin/proteasome-mediated degradation of geminin. Taken together, our study provided a novel link between Id1 and PcG proteins and suggested that Id1 may contribute to tumor development through PcG-mediated epigenetic regulation.
Qian
T
T
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Lee
J-Y
JY
Park
J-H
JH
Kim
H-J
HJ
Kong
G
G
D015153:Blotting, Western; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000235:genetics; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
C069077:BMI1 protein, human; D004268:DNA-Binding Proteins; D006657:Histones; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D009687:Nuclear Proteins; C489348:PCGF2 protein, human; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D063150:Polycomb Repressive Complex 1; C489841:RNF2 protein, human; D044767:Ubiquitin-Protein Ligases