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

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 sho...

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Autores principales:	Lan K Nguyen, Javier Muñoz-García, Helene Maccario, Aaron Ciechanover, Walter Kolch, Boris N Kholodenko
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/aafeecf9ac4742dd92a9142aa127ff1f
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spelling	oai:doaj.org-article:aafeecf9ac4742dd92a9142aa127ff1f2021-11-18T05:51:43ZSwitches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.1553-734X1553-735810.1371/journal.pcbi.1002317https://doaj.org/article/aafeecf9ac4742dd92a9142aa127ff1f2011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22194680/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358In 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.Lan K NguyenJavier Muñoz-GarcíaHelene MaccarioAaron CiechanoverWalter KolchBoris N KholodenkoPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 12, p e1002317 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Lan K Nguyen Javier Muñoz-García Helene Maccario Aaron Ciechanover Walter Kolch Boris N Kholodenko Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.
description	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.
format	article
author	Lan K Nguyen Javier Muñoz-García Helene Maccario Aaron Ciechanover Walter Kolch Boris N Kholodenko
author_facet	Lan K Nguyen Javier Muñoz-García Helene Maccario Aaron Ciechanover Walter Kolch Boris N Kholodenko
author_sort	Lan K Nguyen
title	Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.
title_short	Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.
title_full	Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.
title_fullStr	Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.
title_full_unstemmed	Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.
title_sort	switches, excitable responses and oscillations in the ring1b/bmi1 ubiquitination system.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/aafeecf9ac4742dd92a9142aa127ff1f
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Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.

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