| Title | Phosphorylation Regulates Mycobacterial Proteasome |
|---|---|
| Author | Tripti Anandan1, Jaeil Han1, Heather Baun1, Seeta Nyayapathy1, Jacob T. Brown2, Rebekah L. Dial2, Juan A. Moltalvo2, Min-Seon Kim1, Seung Hwan Yang3, Donald R. Ronning3, Robert N. Husson4, Joowon Suh3*, and Choong-Min Kang2* |
| Address | 1Department of Biological Science, Wayne State University, Detroit, MI 48202, USA, 2Department of Biological Sciences, California State University, Stanislaus, Turlock, CA 95382, USA, 3Division of Bioscience and Bioinformatics, Myongji University, Yongin 449-728, Republic of Korea, 4Division of Infectious Diseases, Children’s Hospital Boston, Harvard Medical School Boston, MA 02115, USA |
| Bibliography | Journal of Microbiology, 52(9),743–754, 2014, |
| DOI | 10.1007/s12275-014-4416-2 |
| Key Words | Mycobacterium tuberculosis, proteasome, phosphorylation |
| 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. |