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The role of ubiquitylation in immune defence and pathogen evasion

Nature Reviews Immunology volume 12, pages 35–48 (2012)Cite this article

Subjects

Key Points

  • Ubiquitylation has important roles in innate immune signalling pathways triggered by pattern recognition receptors.

  • Ubiquitylation is used by the macroautophagy system for the delivery and clearance of cargos containing microorganisms.

  • Ubiquitylation controls the expression levels of MHC molecules and, hence, antigen presentation.

  • Ubiquitylation regulates signalling pathways in B cells and T cells.

  • Pathogens exploit the ubiquitylation system to evade immune surveillance.

Abstract

Ubiquitylation is a widely used post-translational protein modification that regulates many biological processes, including immune responses. The role of ubiquitin in immune regulation was originally uncovered through studies of antigen presentation and the nuclear factor-κB family of transcription factors, which orchestrate host defence against microorganisms. Recent studies have revealed crucial roles of ubiquitylation in many aspects of the immune system, including innate and adaptive immunity and antimicrobial autophagy. In addition, mounting evidence indicates that microbial pathogens exploit the ubiquitin pathway to evade the host immune system. Here, we review recent advances on the role of ubiquitylation in host defence and pathogen evasion.

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Figure 1: Ubiquitin-mediated signalling in TLR and IL-1R pathways.
Figure 2: Different types of polyubiquitylation in the TLR4 signalling pathways.
Figure 3: Roles of ubiquitylation in diverse PRR signalling pathways.
Figure 4: Ubiquitin adaptor proteins mediate selective autophagy of pathogens.
Figure 5: Ubiquitylation controls the expression of MHC molecules.
Figure 6: Ubiquitin E3 ligases regulate TCR signalling.

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Acknowledgements

Research in the Chen laboratory is supported by grants from the US National Institutes of Health, the Cancer Prevention and Research Institute of Texas and the Welch Foundation. Z.J.C. is an Investigator of Howard Hughes Medical Institute.

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  1. Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, 75390-9148, Texas, USA

    Xiaomo Jiang & Zhijian J. Chen

  2. Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, 75390-9148, Texas, USA

    Zhijian J. Chen

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Glossary

Non-canonical NF-κB signalling

An NF-κB activation pathway that processes the NF-κB precursor p100 into p52, uses an NF-κB dimer containing p52 and REL-B subunits, and occurs during B cell maturation and activation. By contrast, canonical NF-κB signalling involves the degradation of IκB and the activation of NF-κB dimers comprising p65 (also known as REL-A), c-REL and p50.

Gene flow

The transfer of genes from one population to another, or across species.

Convergent evolution

The process by which lineages that are not closely related in evolutionary terms independently acquire similar traits.

Sumoylation

A type of protein modification in which the ubiquitin-like protein SUMO is covalently attached to target proteins by an enzymatic cascade that is analogous to that involved in ubiquitylation.

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Jiang, X., Chen, Z. The role of ubiquitylation in immune defence and pathogen evasion. Nat Rev Immunol 12, 35–48 (2012). https://doi.org/10.1038/nri3111

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