LUBAC-synthesized Linear Ubiquitin Chains Restrict Cytosol-invading Bacteria by Activating Autophagy and NF-κB

Overview

Journal Nat Microbiol

Specialties Microbiology
Parasitology

Date 2017 May 9

PMID 28481331

Citations 123

Authors

Jessica Noad

Alexander von der Malsburg

Claudio Pathe

Martin A Michel

David Komander

Felix Randow

Affiliations

Soon will be listed here.

Abstract

Cell-autonomous immunity relies on the ubiquitin coat surrounding cytosol-invading bacteria functioning as an 'eat-me' signal for xenophagy. The origin, composition and precise mode of action of the ubiquitin coat remain incompletely understood. Here, by studying Salmonella Typhimurium, we show that the E3 ligase LUBAC generates linear (M1-linked) polyubiquitin patches in the ubiquitin coat, which serve as antibacterial and pro-inflammatory signalling platforms. LUBAC is recruited via its subunit HOIP to bacterial surfaces that are no longer shielded by host membranes and are already displaying ubiquitin, suggesting that LUBAC amplifies and refashions the ubiquitin coat. LUBAC-synthesized polyubiquitin recruits Optineurin and Nemo for xenophagy and local activation of NF-κB, respectively, which independently restrict bacterial proliferation. In contrast, the professional cytosol-dwelling Shigella flexneri escapes from LUBAC-mediated restriction through the antagonizing effects of the effector E3 ligase IpaH1.4 on deposition of M1-linked polyubiquitin and subsequent recruitment of Nemo and Optineurin. We conclude that LUBAC-synthesized M1-linked ubiquitin transforms bacterial surfaces into signalling platforms for antibacterial immunity reminiscent of antiviral assemblies on mitochondria.

Citing Articles

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Manipulating autophagic degradation in human diseases: from mechanisms to interventions.

Zhang Y, Liu X, Klionsky D, Lu B, Zhong Q Life Med. 2025; 1(2):120-148.

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Ubiquitin and Ubiquitin-Like Modifications in Organelle Stress Signaling: Ub, Ub, Ub, Ub, Stayin' Alive, Stayin' Alive.

Lafont E, Chevet E Bioessays. 2024; 47(2):e202400230.

PMID: 39600056 PMC: 11755688. DOI: 10.1002/bies.202400230.

The effector IpaH1.4 facilitates RNF213 degradation and protects cytosolic bacteria against interferon-induced ubiquitylation.

Saavedra-Sanchez L, Dickinson M, Apte S, Zhang Y, de Jong M, Skavicus S bioRxiv. 2024; .

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Secondary interactions in ubiquitin-binding domains achieve linkage or substrate specificity.

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