AI Article Synopsis
- Polyubiquitination is key in the protein degradation process and also regulates various intracellular events, with different ubiquitin linkages leading to diverse structures.
- Linear ubiquitination, an uncommon modification, is triggered by inflammatory stimuli and activates the NF-κB signaling pathway, which helps protect cells from death during inflammation.
- This review highlights how linear ubiquitination plays a crucial role in adapting to inflammatory conditions, affecting both normal physiological processes and the development of inflammatory diseases.
Article Abstract
In addition to its role in the ubiquitin-proteasome system of protein degradation, polyubiquitination is involved in the regulation of intracellular events. Depending on the type of ubiquitin-ubiquitin linkage used, polyubiquitin can assume several types of structures. The spatiotemporal dynamics of polyubiquitin involve multiple adaptor proteins and induce different downstream outputs. Linear ubiquitination, in which the N-terminal methionine on the acceptor ubiquitin serves as the site for ubiquitin-ubiquitin conjugation, is a rare and atypical type of polyubiquitin modification. The production of linear ubiquitin chains is dependent on various external inflammatory stimuli and leads to the transient activation of the downstream NF-κB signalling pathway. This in turn suppresses extrinsic programmed cell death signals and protects cells from activation-induced cell death under inflammatory conditions. Recent evidence has revealed the role of linear ubiquitination in various biological processes under both physiological and pathological conditions. This led us to propose that linear ubiquitination may be pivotal in the 'inflammatory adaptation' of cells, and consequently in tissue homeostasis and inflammatory disease. In this review, we focused on the physiological and pathophysiological roles of linear ubiquitination in vivo in response to a changing inflammatory microenvironment.
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