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Cell Death and Inflammation - A Vital but Dangerous Liaison
Nieves Peltzer1, Henning Walczak1
1Centre for Cell Death, Cancer, and Inflammation, UCL Cancer Institute, University College London, 72 Huntley Street, London WC1E 6BT, UK.
Abstract:
The immune system has developed multiple ways to fight infection. Yet, it is constantly tasked with overcoming newly developing pathogenic mechanisms of resistance to host immunity. In most mammals, the stimulation of both innate and adaptive immune receptors can result in gene activation and cell death induction by apoptosis and necroptosis. RIPK1 and RIPK3 are key mediators of necroptosis; however, new findings support their role in the regulation of cell death-independent proinflammatory signaling. We discuss here the biological functions of RIPK1 and RIPK3, how they regulate cell death and inflammation, and the interplay between them. Finally, we discuss recent advances in our knowledge of linear ubiquitination which, alongside RIPK3 and caspase-8, exerts regulatory functions on RIPK1-mediated inflammation. Together, this review examines the complex interplay between RIPK1, RIPK3, and LUBAC that is important in regulating cell death and inflammatory signaling.
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