The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity

Mol Cell. 2006 Dec 8;24(5):701-711. doi: 10.1016/j.molcel.2006.10.022.

Abstract

Polycomb complexes mediate gene silencing, in part by modifying histones. Ring1B and Bmi1 are RING finger proteins that are members of the Polycomb repressive complex 1 (PRC1). Ring1B is an E3 that mediates its own polyubiquitination and monoubiquitination of histone H2A. In contrast, Bmi1 has no self-ubiquitinating activity. We show that unlike other RING finger proteins that are believed to mediate their own ubiquitination and degradation, Ring1B and Bmi1 are degraded by an exogenous E3, independent of their RING domain. The RING domains of both proteins mediate their association and subsequent stabilization. Consistent with the nonproteolytic self-ligase activity of Ring1B, it generates atypical mixed K6-, K27-, and K48-based polyubiquitin chains, which require the presence of all these lysine residues on the same ubiquitin molecule. The modification is required for Ring1B ability to monoubiquitinate H2A in vitro, unraveling an as yet undescribed mechanism for ligase activation via noncanonical self-ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cells, Cultured
  • Chlorocebus aethiops
  • DNA-Binding Proteins / metabolism*
  • HeLa Cells
  • Histones / metabolism*
  • Humans
  • Nuclear Proteins / metabolism
  • Polycomb Repressive Complex 1
  • Proteasome Endopeptidase Complex / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Repressor Proteins / metabolism
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • BMI1 protein, human
  • DNA-Binding Proteins
  • Histones
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Repressor Proteins
  • Ubiquitin
  • Polycomb Repressive Complex 1
  • RNF2 protein, human
  • Ubiquitin-Protein Ligases
  • Proteasome Endopeptidase Complex