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Switches, Excitable Responses and Oscillations in the Ring1B/Bmi1 Ubiquitination System
Date Issued
2011-12-15
Date Available
2013-11-29T09:41:08Z
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.
Other Sponsorship
SFI Grant No. 06/CE/B1129, NIH grant GM059570, the Juan de la Cierva program and grant No. FIS2009-12964-C05-01.
Type of Material
Journal Article
Publisher
Public Library of Science
Journal
PLoS Computational Biology
Volume
7
Issue
12
Start Page
e1002317
Copyright (Published Version)
2011 Public Library of Science
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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