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Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis
Unlike most bacterial species, Mycobacterium tuberculosis depends on the Clp proteolysis system for survival even in in vitro conditions. We hypothesized that Clp is required for the physiologic turnover of mycobacterial proteins whose accumulation is deleterious to bacterial growth and survival. To...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946367/ https://www.ncbi.nlm.nih.gov/pubmed/24603869 http://dx.doi.org/10.1371/journal.ppat.1003994 |
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author | Raju, Ravikiran M. Jedrychowski, Mark P. Wei, Jun-Rong Pinkham, Jessica T. Park, Annie S. O'Brien, Kathryn Rehren, German Schnappinger, Dirk Gygi, Steven P. Rubin, Eric J. |
author_facet | Raju, Ravikiran M. Jedrychowski, Mark P. Wei, Jun-Rong Pinkham, Jessica T. Park, Annie S. O'Brien, Kathryn Rehren, German Schnappinger, Dirk Gygi, Steven P. Rubin, Eric J. |
author_sort | Raju, Ravikiran M. |
collection | PubMed |
description | Unlike most bacterial species, Mycobacterium tuberculosis depends on the Clp proteolysis system for survival even in in vitro conditions. We hypothesized that Clp is required for the physiologic turnover of mycobacterial proteins whose accumulation is deleterious to bacterial growth and survival. To identify cellular substrates, we employed quantitative proteomics and transcriptomics to identify the set of proteins that accumulated upon the loss of functional Clp protease. Among the set of potential Clp substrates uncovered, we were able to unambiguously identify WhiB1, an essential transcriptional repressor capable of auto-repression, as a substrate of the mycobacterial Clp protease. Dysregulation of WhiB1 turnover had a toxic effect that was not rescued by repression of whiB1 transcription. Thus, under normal growth conditions, Clp protease is the predominant regulatory check on the levels of potentially toxic cellular proteins. Our findings add to the growing evidence of how post-translational regulation plays a critical role in the regulation of bacterial physiology. |
format | Online Article Text |
id | pubmed-3946367 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39463672014-03-12 Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis Raju, Ravikiran M. Jedrychowski, Mark P. Wei, Jun-Rong Pinkham, Jessica T. Park, Annie S. O'Brien, Kathryn Rehren, German Schnappinger, Dirk Gygi, Steven P. Rubin, Eric J. PLoS Pathog Research Article Unlike most bacterial species, Mycobacterium tuberculosis depends on the Clp proteolysis system for survival even in in vitro conditions. We hypothesized that Clp is required for the physiologic turnover of mycobacterial proteins whose accumulation is deleterious to bacterial growth and survival. To identify cellular substrates, we employed quantitative proteomics and transcriptomics to identify the set of proteins that accumulated upon the loss of functional Clp protease. Among the set of potential Clp substrates uncovered, we were able to unambiguously identify WhiB1, an essential transcriptional repressor capable of auto-repression, as a substrate of the mycobacterial Clp protease. Dysregulation of WhiB1 turnover had a toxic effect that was not rescued by repression of whiB1 transcription. Thus, under normal growth conditions, Clp protease is the predominant regulatory check on the levels of potentially toxic cellular proteins. Our findings add to the growing evidence of how post-translational regulation plays a critical role in the regulation of bacterial physiology. Public Library of Science 2014-03-06 /pmc/articles/PMC3946367/ /pubmed/24603869 http://dx.doi.org/10.1371/journal.ppat.1003994 Text en © 2014 Raju et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Raju, Ravikiran M. Jedrychowski, Mark P. Wei, Jun-Rong Pinkham, Jessica T. Park, Annie S. O'Brien, Kathryn Rehren, German Schnappinger, Dirk Gygi, Steven P. Rubin, Eric J. Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis |
title | Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis
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title_full | Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis
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title_fullStr | Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis
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title_full_unstemmed | Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis
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title_short | Post-Translational Regulation via Clp Protease Is Critical for Survival of Mycobacterium tuberculosis
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title_sort | post-translational regulation via clp protease is critical for survival of mycobacterium tuberculosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3946367/ https://www.ncbi.nlm.nih.gov/pubmed/24603869 http://dx.doi.org/10.1371/journal.ppat.1003994 |
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