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. 2019 Jan;33(1):683-695.
doi: 10.1096/fj.201800397R. Epub 2018 Jul 24.

RYBP modulates stability and function of Ring1B through targeting UBE3A

Meng Li  1 , Shiqiang Zhang  1 , Wen Zhao  1 , Congcong Hou  1 , Xiaoli Ma  1 , Xuekun Li  2 , Bingren Huang  1 , Hong Chen  1 , Deng Chen  1
Affiliations

RYBP modulates stability and function of Ring1B through targeting UBE3A

Meng Li et al. FASEB J. 2019 Jan.

Abstract

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 Ring1B 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.

Keywords: polycomb-repressive complex 1; proteasome; protein interaction; ubiquitination.

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