Switches, excitable responses and oscillations in the ring1B/Bmi1 ubiquitination system

Lan K. Nguyen, Javier Muñoz-García, Helene Maccario, Aaron Ciechanover, Walter Kolch, Boris N. Kholodenko

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

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.

Original languageEnglish
Article numbere1002317
JournalPLoS Computational Biology
Volume7
Issue number12
DOIs
StatePublished - 1 Dec 2011

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Ubiquitination
Ligases
ligases
oscillation
Switch
Switches
Oscillation
Overshoot
Genes
histones
Histones
Degradation
degradation
gene
Polycomb-Group Proteins
Polyubiquitin
Gene
Data Modeling
Computational Modeling
Catalyst activity

Cite this

Nguyen, Lan K. ; Muñoz-García, Javier ; Maccario, Helene ; Ciechanover, Aaron ; Kolch, Walter ; Kholodenko, Boris N. / Switches, excitable responses and oscillations in the ring1B/Bmi1 ubiquitination system. In: PLoS Computational Biology. 2011 ; Vol. 7, No. 12.
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Switches, excitable responses and oscillations in the ring1B/Bmi1 ubiquitination system. / Nguyen, Lan K.; Muñoz-García, Javier; Maccario, Helene; Ciechanover, Aaron; Kolch, Walter; Kholodenko, Boris N.

In: PLoS Computational Biology, Vol. 7, No. 12, e1002317, 01.12.2011.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Kolch, Walter

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