Switches, Excitable Responses and Oscillations in the Ring1B/Bmi1 Ubiquitination System

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Title: Switches, Excitable Responses and Oscillations in the Ring1B/Bmi1 Ubiquitination System
Authors: Nguyen, Lan K.
Muñoz-García, Javier
Maccario, Helene
et al.
Permanent link: http://hdl.handle.net/10197/5044
Date: 15-Dec-2011
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.
Type of material: Journal Article
Publisher: Public Library of Science
Copyright (published version): 2011 Public Library of Science
Keywords: ubiquitinationdynamic control of Ring1Bgene silencing
DOI: 10.1371/journal.pcbi.1002317
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

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