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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-12-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22194680/?tool=EBI |
| _version_ | 1828901695030034432 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-13T16:03:42Z |
| format | Article |
| id | doaj.art-aafeecf9ac4742dd92a9142aa127ff1f |
| institution | Directory Open Access Journal |
| issn | 1553-734X 1553-7358 |
| language | English |
| last_indexed | 2024-12-13T16:03:42Z |
| publishDate | 2011-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj.art-aafeecf9ac4742dd92a9142aa127ff1f2022-12-21T23:39:06ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582011-12-01712e100231710.1371/journal.pcbi.1002317Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system.Lan K NguyenJavier Muñoz-GarcíaHelene MaccarioAaron CiechanoverWalter KolchBoris N KholodenkoIn 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.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22194680/?tool=EBI |
| spellingShingle | 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. PLoS Computational Biology |
| title | 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_short | Switches, excitable responses and oscillations in the Ring1B/Bmi1 ubiquitination system. |
| title_sort | switches excitable responses and oscillations in the ring1b bmi1 ubiquitination system |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22194680/?tool=EBI |
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