Phosphorylation regulates mycobacterial proteasome

Tripti Anandan, Jaeil Han, Heather Baun, Seeta Nyayapathy, Jacob T. Brown, Rebekah L. Dial, Juan A. Moltalvo, Min Seon Kim, Seung Hwan Yang, Donald R. Ronning, Robert N. Husson, Joowon Suh, Choong Min Kang

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Mycobacterium tuberculosis possesses a proteasome system that is required for the microbe to resist elimination by the host immune system. Despite the importance of the proteasome in the pathogenesis of tuberculosis, the molecular mechanisms by which proteasome activity is controlled remain largely unknown. Here, we demonstrate that the α-subunit (PrcA) of the M. tuberculosis proteasome is phosphorylated by the PknB kinase at three threonine residues (T84, T202, and T178) in a sequential manner. Furthermore, the proteasome with phosphorylated PrcA enhances the degradation of Ino1, a known proteasomal substrate, suggesting that PknB regulates the proteolytic activity of the proteasome. Previous studies showed that depletion of the proteasome and the proteasome-associated proteins decreases resistance to reactive nitrogen intermediates (RNIs) but increases resistance to hydrogen peroxide (H2O2). Here we show that PknA phosphorylation of unprocessed proteasome β-subunit (pre-PrcB) and α-subunit reduces the assembly of the proteasome complex and thereby enhances the mycobacterial resistance to H2O2 and that H2O2 stress diminishes the formation of the proteasome complex in a PknA-dependent manner. These findings indicate that phosphorylation of the M. tuberculosis proteasome not only modulates proteolytic activity of the proteasome, but also affects the proteasome complex formation contributing to the survival of M. tuberculosis under oxidative stress conditions.

Original languageEnglish (US)
Pages (from-to)743-754
Number of pages12
JournalJournal of Microbiology
Volume52
Issue number9
DOIs
StatePublished - Sep 1 2014

Keywords

  • Mycobacterium tuberculosis
  • phosphorylation
  • proteasome

ASJC Scopus subject areas

  • Microbiology
  • Applied Microbiology and Biotechnology

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    Anandan, T., Han, J., Baun, H., Nyayapathy, S., Brown, J. T., Dial, R. L., Moltalvo, J. A., Kim, M. S., Yang, S. H., Ronning, D. R., Husson, R. N., Suh, J., & Kang, C. M. (2014). Phosphorylation regulates mycobacterial proteasome. Journal of Microbiology, 52(9), 743-754. https://doi.org/10.1007/s12275-014-4416-2