Identification of a depupylation regulator for an essential enzyme in Mycobacterium tuberculosis

ABSTRACT: Mycobacterium tuberculosis can use a proteasome to degrade proteins when they are post-translationally modified with prokaryotic ubiquitin-like protein (Pup). While pupylation is reversible, mechanisms regulating depupylation have not been identified. Here, we identify a depupylation regulator, CoaX, a pseudo-pantothenate kinase. Pantothenate synthesis enzymes were more abundant in a ∆coaX mutant, including PanB, a substrate of the Pup-proteasome system. Media supplementation with pantothenate decreased PanB levels in a coaX and Pup-proteasome system-dependent manner. In vitro, CoaX accelerated depupylation of Pup~PanB, while addition of pantothenate inhibited this reaction. Collectively, we propose CoaX contributes to proteasomal degradation of PanB by modulating depupylation of Pup~PanB in response to pantothenate levels.

ORGANISM(S): Mycobacterium tuberculosis

PROVIDER: GSE260838 | GEO | 2024/11/01

REPOSITORIES: GEO