The bacterial proteasome regulation mechanisms

Intracellular protein degradation is essential for the proper functioning of cells. Because proteolysis irreversibly destroys proteins, it has evolved to avoid random, uncontrolled degradation by meticulous regulation. Thus, understanding the regulatory mechanisms that control proteolytic systems is often a challenging task. The bacterial analog of the ubiquitin-proteasome system is called the Pup-proteasome system (PPS) and is an attractive research model for proteolysis owing to its relative simplicity. Although it was shown that the PPS is regulated in response to external stimuli, how the proteasome is activated and what signals mediate degradation in response to external stimulations and stressors remain poorly understood. Despite intensive research on this system over the past two decades. We decided to approach this issue by initially characterizing the proteasomal components by examining their expression pattern. This characterization revealed changes in proteasomal components levels in different stages of bacterial growth followed by proteasomal stimulation and accelerated degradation. A deeper exploration of this aspect revealed post-translational regulation of the proteasomal core particle and an indication of self-degradation via the Pup-proteasome pathway. In addition, it appears that its levels are limiting for proteasomal activity among additional unknown factors. The PPS is important to the virulence of Mycobacterium tuberculosis. As M. tuberculosis is the deadliest bacterial pathogen on a global scale, understanding the major regulatory factors of the proteasome has the potential to impact the lives of many. Specifically, this research can facilitate the development of new drugs that disrupt PPS function and consequently interfere with M. tuberculosis virulence and survival.