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...

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Autores principales:	Ravikiran M Raju, Mark P Jedrychowski, Jun-Rong Wei, Jessica T Pinkham, Annie S Park, Kathryn O'Brien, German Rehren, Dirk Schnappinger, Steven P Gygi, Eric J Rubin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/bdaac5ae17c84c90bb2fac362fa26bd5
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spelling	oai:doaj.org-article:bdaac5ae17c84c90bb2fac362fa26bd52021-11-18T06:06:53ZPost-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.1553-73661553-737410.1371/journal.ppat.1003994https://doaj.org/article/bdaac5ae17c84c90bb2fac362fa26bd52014-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24603869/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Unlike 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.Ravikiran M RajuMark P JedrychowskiJun-Rong WeiJessica T PinkhamAnnie S ParkKathryn O'BrienGerman RehrenDirk SchnappingerSteven P GygiEric J RubinPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 10, Iss 3, p e1003994 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Ravikiran M Raju Mark P Jedrychowski Jun-Rong Wei Jessica T Pinkham Annie S Park Kathryn O'Brien German Rehren Dirk Schnappinger Steven P Gygi Eric J Rubin Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.
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	article
author	Ravikiran M Raju Mark P Jedrychowski Jun-Rong Wei Jessica T Pinkham Annie S Park Kathryn O'Brien German Rehren Dirk Schnappinger Steven P Gygi Eric J Rubin
author_facet	Ravikiran M Raju Mark P Jedrychowski Jun-Rong Wei Jessica T Pinkham Annie S Park Kathryn O'Brien German Rehren Dirk Schnappinger Steven P Gygi Eric J Rubin
author_sort	Ravikiran M Raju
title	Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.
title_short	Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.
title_full	Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.
title_fullStr	Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.
title_full_unstemmed	Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.
title_sort	post-translational regulation via clp protease is critical for survival of mycobacterium tuberculosis.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/bdaac5ae17c84c90bb2fac362fa26bd5
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Post-translational regulation via Clp protease is critical for survival of Mycobacterium tuberculosis.

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