CG4968 positively regulates the immune deficiency pathway by targeting Imd protein in Drosophila

PeerJ. 2023 Feb 7:11:e14870. doi: 10.7717/peerj.14870. eCollection 2023.

Abstract

Drosophila melanogaster relies solely on innate immunity to defend against various microbial pathogens. Although it is well-known that the adaptor protein Imd undergoes K63-linked ubiquitination to activate the downstream signaling cascades, its involvement with K48-linked ubiquitination and what is responsible for controlling this modification remain largely unknown. In this study, we explored the immunological function of CG4968, which encodes a typical ovarian tumour-associated protease (OTU)-type deubiquitinase (Dub) in flies. Our in vitro and vivo evidence demonstrated that CG4968 plays a positive role in governing the immune deficiency (IMD), but not the Toll innate immune response in an OTU domain-dependent manner. Mechanistically, we found that CG4968 is associated with Imd to restrict its K48-linked ubiquitination, thereby contributing to its turnover. Collectively, our study uncovered a novel regulatory mechanism involving the K48-linked ubiquitination of Imd in Drosophila innate immunity.

Keywords: CG4968; Drosophila melanogaster; Dub; Imd; K48-linked ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins* / genetics
  • Drosophila melanogaster* / genetics
  • Immunity, Innate*
  • NF-kappa B / metabolism
  • Signal Transduction

Substances

  • Drosophila Proteins
  • NF-kappa B

Grants and funding

This research was funded by Anhui Provincial Natural Science Foundation, grant number 2008085J14, and Anhui Agricultural University 2022 College Students Innovation and Entrepreneurship Training Science and Technology Project, grant number X202210364712. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.