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RYBP modulates stability and function of Ring1B through targeting UBE3A
Author(s) -
Li Meng,
Zhang Shiqiang,
Zhao Wen,
Hou Congcong,
Ma Xiaoli,
Li Xuekun,
Huang Bingren,
Chen Hong,
Chen Deng
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201800397r
Subject(s) - ubiquitin ligase , ube3a , ubiquitin , microbiology and biotechnology , repressor , chemistry , f box protein , biochemistry , biology , gene , gene expression
Ring1 and yin yang 1–binding protein (RYBP) are central components of noncanonical polycomb‐repressive complex 1 (nc‐PRC1), which represses target gene expression and is required for normal organismal development. However, the molecular function of RYBP in this complex is obscure. In this study, we showed that RYBP inhibits the polyubiquitination‐mediated proteasomal degradation of RingIB independently of its ubiquitin (Ub)‐protein isopeptide ligase (E3) ligase activity, leading to its stabilization and increased catalytic activity toward monoubiquitination of histone H2A at lysine 119. Mechanistic dissection further disclosed that RYBP directly binds to ubiquitin protein ligase E3A (UBE3A) to promote its ubiquitination and proteasomal degradation in an autoubiquitination‐independent manner. The resultant reduction of UBE3A protein level alleviates its effect on ubiquitination‐mediated degradation of Ring1B, therefore resulting in increased stability and enhanced transcriptional repressor activity on its target genes. Thus, our current findings lay a foundation for understanding how RYBP functions in nc‐PRC1 complexes, which is involved in development, stem cell maintenance, and carcinogenesis.—Li, M., Zhang, S., Zhao, W., Hou, C., Ma, X., Li, X., Huang, B., Chen, H., Chen, D. RYBP modulates stability and function of Ring1B through targeting UBE3A. FASEB J. 33, 683–695 (2019). www.fasebj.org