Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.

Authors

Lan K Nguyen, Systems Biology Ireland, University College Dublin, Belfield, Dublin, IrelandFollow
Javier Muñoz-García, Systems Biology Ireland, University College Dublin, Belfield, Dublin, IrelandFollow
Helene Maccario, Systems Biology Ireland, University College Dublin, Belfield, Dublin, Ireland
Aaron Ciechanover, Cancer and Vascular Biology Research Center, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Bat Galim, Haifa, Israel
Walter Kolch, Systems Biology Ireland, University College Dublin, Belfield, Dublin, IrelandFollow
Boris N Kholodenko, Systems Biology Ireland, University College Dublin, Belfield, Dublin, Ireland; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow

Document Type

Article

Publication Date

12-1-2011

Comments

This article has been peer reviewed and is published in PLoS One 2011, 7(12). The published version is available at DOI: 10.1371/journal.pcbi.1002317. © Public Library of Science

Abstract

In an active, self-ubiquitinated state, the Ring1B ligase monoubiquitinates histone H2A playing a critical role in Polycomb-mediated gene silencing. Following ubiquitination by external ligases, Ring1B is targeted for proteosomal degradation. Using biochemical data and computational modeling, we show that the Ring1B ligase can exhibit abrupt switches, overshoot transitions and self-perpetuating oscillations between its distinct ubiquitination and activity states. These different Ring1B states display canonical or multiply branched, atypical polyubiquitin chains and involve association with the Polycomb-group protein Bmi1. Bistable switches and oscillations may lead to all-or-none histone H2A monoubiquitination rates and result in discrete periods of gene (in)activity. Switches, overshoots and oscillations in Ring1B catalytic activity and proteosomal degradation are controlled by the abundances of Bmi1 and Ring1B, and the activities and abundances of external ligases and deubiquitinases, such as E6-AP and USP7.

Recommended Citation

Nguyen, Lan K; Muñoz-García, Javier; Maccario, Helene; Ciechanover, Aaron; Kolch, Walter; and Kholodenko, Boris N, "Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system." (2011). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 71.
https://jdc.jefferson.edu/pacbfp/71

PubMed ID

22194680