PE_PGRS38 Interaction With HAUSP Downregulates Antimycobacterial Host Defense via TRAF6
- Title
- PE_PGRS38 Interaction With HAUSP Downregulates Antimycobacterial Host Defense via TRAF6
- Author
- 양철수
- Keywords
- Mycobacterium tuberculosis PE_PGRS38; Mycobacterium smegmatis; HAUSP; TRAF6; Macrophages; Ubiquitination
- Issue Date
- 2022-04
- Publisher
- Frontiers Media S.A.
- Citation
- Frontiers in Immunology, v. 13.0, article no. 862628,
- Abstract
- Mycobacterium tuberculosis (Mtb) is the causative pathogen of tuberculosis (TB), which manipulates the host immunity to ensure survival and colonization in the host. Mtb possess a unique family of proteins, named PE_PGRS, associated with Mtb pathogenesis. Thus, elucidation of the functions of PE_PGRS proteins is necessary to understand TB pathogenesis. Here, we investigated the role of PE_PGRS38 binding to herpesvirus-associated ubiquitin-specific protease (HAUSP, USP7) in regulating the activity of various substrate proteins by modulating their state of ubiquitination. We constructed the recombinant PE_PGRS38 expressed in M. smegmatis (Ms_PE_PGRS38) to investigate the role of PE_PGRS38. We found that Ms_PE_PGRS38 regulated the cytokine levels in murine bone marrow-derived macrophages by inhibiting the deubiquitination of tumor necrosis factor receptor-associated factor (TRAF) 6 by HAUSP. Furthermore, the PE domain in PE_PGRS38 was identified as essential for mediating TRAF6 deubiquitination. Ms_PE_PGRS38 increased the intracellular burden of bacteria by manipulating cytokine levels in vitro and in vivo. Overall, we revealed that the interplay between HAUSP and PE_PGRS38 regulated the inflammatory response to increase the survival of mycobacteria.
- URI
- https://www.frontiersin.org/articles/10.3389/fimmu.2022.862628/fullhttps://repository.hanyang.ac.kr/handle/20.500.11754/177540
- ISSN
- 1664-3224;1664-3224
- DOI
- 10.3389/fimmu.2022.862628
- Appears in Collections:
- COLLEGE OF SCIENCE AND CONVERGENCE TECHNOLOGY[E](과학기술융합대학) > MOLECULAR AND LIFE SCIENCE(분자생명과학과) > Articles
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