Aim: Mycobacterium tuberculosis possesses an intracellular tagging and degradation system, which has emerged as a target for development of anti-tuberculosis agents. In this system, PafA is the ligase that marks proteins for degradation by their covalent modification with a protein modifier. Here, we studied pafA transcriptional regulation, which remained elusive despite its importance for M. tuberculosis virulence.
Materials & methods: Working with Mycobacterium smegmatis, a mycobacterial model organism, we examined the involvement of the global regulators PafB and PafC in pafA regulation.
Results: PafBC activated pafA transcription following DNA damage, resulting in efficient cellular recovery.
Conclusion: The results unraveled the involvement of PafBC in pafA transcription, and revealed the importance of proper PafA regulation in mycobacterial physiology.
Keywords: PafA; PafB; PafC; Pup; proteasome; proteolysis.