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BMI1–RING1B is an autoinhibited RING E3 ubiquitin ligase

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  • Asad M. Taherbhoy

    (Genentech Inc.
    Present address: Nurix, Inc., 1700 Owens St. Suite 290, San Francisco, California 94158, USA.)

  • Oscar W. Huang

    (Genentech Inc.)

  • Andrea G. Cochran

    (Genentech Inc.)

Abstract

Polycomb repressive complex 1 (PRC1) is required for ubiquitination of histone H2A lysine 119, an epigenetic mark associated with repression of genes important in developmental regulation. The E3 ligase activity of PRC1 resides in the RING1A/B subunit when paired with one of six PCGF partners. The best known of these is the oncogene BMI1/PCGF4. We find that canonical PRC1 E3 ligases such as PCGF4–RING1B have intrinsically very low enzymatic activity compared with non-canonical PRC1 RING dimers. The structure of a high-activity variant in complex with E2 (PCGF5–RING1B–UbcH5c) reveals only subtle differences from an earlier PCGF4 complex structure. However, two charged residues present in the modelled interface with E2-conjugated ubiquitin prove critical: in BMI1/PCGF4, these residues form a salt bridge that may limit efficient ubiquitin transfer. The intrinsically low activity of the PCGF4–RING1B heterodimer is offset by a relatively favourable interaction with nucleosome substrates, resulting in an efficient site-specific monoubiquitination.

Suggested Citation

  • Asad M. Taherbhoy & Oscar W. Huang & Andrea G. Cochran, 2015. "BMI1–RING1B is an autoinhibited RING E3 ubiquitin ligase," Nature Communications, Nature, vol. 6(1), pages 1-13, November.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8621
    DOI: 10.1038/ncomms8621
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    Cited by:

    1. Yanjiang Liu & Gongcheng Hu & Shengxiong Yang & Mingze Yao & Zicong Liu & Chenghong Yan & Yulin Wen & Wangfang Ping & Juehan Wang & Yawei Song & Xiaotao Dong & Guangjin Pan & Hongjie Yao, 2023. "Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Jorine M. Eeftens & Manya Kapoor & Davide Michieletto & Clifford P. Brangwynne, 2021. "Polycomb condensates can promote epigenetic marks but are not required for sustained chromatin compaction," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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