Title :

The Mycobacterium tuberculosis transcriptional repressor EthR is negatively regulated by Serine/Threonine phosphorylation

Author(s) :

Leiba, Jade [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Carrere-Kremer, Severine [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Blondiaux, Nicolas [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Dimala, Martin Moune [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Wohlkönig, Alexandre [Auteur]
Structural Biology Brussels [SBB]
Baulard, Alain [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Kremer, Laurent [Auteur]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]
Molle, Virginie [Auteur correspondant]
Dynamique des interactions membranaires normales et pathologiques [DIMNP]

Journal title :

Biochemical and Biophysical Research Communications

Pages :

1132-1138

Publisher :

Elsevier

Publication date :

2014-04

ISSN :

0006-291X

English keyword(s) :

EthR
Ethionamide
Mycobacterium
Phosphorylation
Ser/Thr protein kinases

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Bactériologie

English abstract : [en]

Recent efforts have underlined the role of Serine/Threonine Protein Kinases (STPKs) in growth, pathogenesis and cell wall metabolism in mycobacteria. Herein, we demonstrated that the Mycobacterium tuberculosis EthR, a ...
Show more >Recent efforts have underlined the role of Serine/Threonine Protein Kinases (STPKs) in growth, pathogenesis and cell wall metabolism in mycobacteria. Herein, we demonstrated that the Mycobacterium tuberculosis EthR, a transcriptional repressor that regulates the activation process of the antitubercular drug ethionamide (ETH) is a specific substrate of the mycobacterial kinase PknF. ETH is a prodrug that must undergo bioactivation by the monooxygenease EthA to exert its antimycobacterial activity and previous studies reported that EthR represses transcription of ethA by binding to the ethA-ethR intergenic region. Mass spectrometry analyses and site-directed mutagenesis identified a set of four phosphoacceptors, namely Thr2, Thr3, Ser4 and Ser7. This was further supported by the complete loss of PknF-dependent phosphorylation of a phosphoablative EthR mutant protein. Importantly, a phosphomimetic version of EthR, in which all phosphosites were replaced by Asp residues, exhibited markedly decreased DNA-binding activity compared with the wild-type protein. Together, these findings are the first demonstration of EthR phosphorylation and indicate that phosphorylation negatively affects its DNA-binding activity, which may impact ETH resistance levels in M. tb.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

ANR Project :

Identification de régulons sous contrôle de régulateurs phosphorylés et leur rôle dans l'adaptation des mycobacteries dans leur environnement : une approche via "ChIP-on-chip" chez Mycobacterium tuberculosis

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL