Id1 enhances E3 ligase activation of RING1b through PRC1 complex.

Abstract

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 Id-1 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 PRC1 but not PRC2 complex. 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 over-expression 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.