K63 ubiquitination in immune signaling

Ubc13-catalyzed K63 ubiquitination is a major control point for immune signaling. Recent evidence has shown that the control of multiple immune functions, including chronic inflammation, pathogen responses, lymphocyte activation, and regulatory signaling, is altered by K63 ubiquitination. In this review, we detail the novel cellular sensors that are dependent on K63 ubiquitination for their function in the immune signaling network. Many pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can target K63 ubiquitination to inhibit pathogen immune responses; we describe novel details of the pathways involved and sum-marize recent clinically relevant SARS-CoV-2-specific responses. We also discuss recent evidence that regulatory T cell (Treg) versus T helper (T-H) 1 and T(H)17 cell sub-set regulation might involve K63 ubiquitination. Knowledge gaps that merit future investigation and clinically relevant pathways are also addressed.

Automated summary

This review highlights the significance of K63 ubiquitination in immune signaling and its role in regulating various immune functions. It provides insights into the mechanisms by which pathogens, including SARS-CoV-2, suppress immune responses through targeting K63 ubiquitination. The review also discusses recent findings suggesting the involvement of K63 ubiquitination in the regulation of regulatory T cells and T helper cell subsets, and identifies knowledge gaps for future investigation and clinically relevant pathways.