M. tuberculosis intramembrane protease Rip1 controls transcription through three anti-sigma factor substrates Journal Article
| Authors: | Sklar, J. G.; Makinoshima, H.; Schneider, J. S.; Glickman, M. |
| Article Title: | M. tuberculosis intramembrane protease Rip1 controls transcription through three anti-sigma factor substrates |
| Abstract: | Regulated intramembrane proteolysis (RIP) is a mechanism of transmembrane signal transduction that functions through intramembrane proteolysis of substrates. We previously reported that the RIP metalloprotease Rv2869c (Rip1) is a determinant of Mycobacterium tuberculosis (Mtb) cell envelope composition and virulence, but the substrates of Rip1 were undefined. Here we show that Rip1 cleaves three transmembrane anti-sigma factors: anti-SigK, anti-SigL and anti-SigM, negative regulators of Sigma K, L and M. We show that transcriptional activation of katG in response to phenanthroline requires activation of SigK and SigL by Rip1 cleavage of anti-SigK and anti-SigL. We also demonstrate a Rip1-dependent pathway that activates the genes for the mycolic acid biosynthetic enzyme KasA and the resuscitation promoting factor RpfC, but represses the bacterioferritin encoding gene bfrB. Regulation of these three genes by Rip1 is not reproduced by deletion of Sigma K, L or M, either indicating a requirement for multiple Rip1 substrates or additional arms of the Rip1 pathway. These results identify a branched proteolytic signal transduction system in which a single intramembrane protease cleaves three anti-sigma factor substrates to control multiple downstream pathways involved in lipid biosynthesis and defence against oxidative stress. © 2010 Blackwell Publishing Ltd. |
| Keywords: | signal transduction; unclassified drug; gene deletion; nonhuman; protein degradation; membrane proteins; genetic transcription; transcription, genetic; enzyme substrate; gene activation; mycolic acid; mycobacterium tuberculosis; bacterial proteins; amino acid sequence; molecular sequence data; sequence alignment; substrate specificity; gene control; proteinase; genetic code; lipogenesis; gene expression regulation, bacterial; bacterioferritin; katg protein; phenanthroline; protease rip1; sigma factor; metalloproteases |
| Journal Title: | Molecular Microbiology |
| Volume: | 77 |
| Issue: | 3 |
| ISSN: | 0950-382X |
| Publisher: | Blackwell Publishing |
| Date Published: | 2010-08-01 |
| Start Page: | 605 |
| End Page: | 617 |
| Language: | English |
| DOI: | 10.1111/j.1365-2958.2010.07232.x |
| PUBMED: | 20545848 |
| PROVIDER: | scopus |
| PMCID: | PMC3008510 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "CODEN: MOMIE" - "Source: Scopus" |
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