From death receptor to reactive oxygen species and c-Jun N-terminal protein kinase: the receptor-interacting protein 1 odyssey.
Death receptors (DRs) are more than simple killers: they control cell growth, proliferation, and survival, thereby playing a pivotal role in immune and inflammatory responses. Some of these phenomena might be explained by aberrant reactive oxygen species (ROS) production and metabolism, which can lead to oxidative stress. A key signaling molecule of DR-initiated intracellular pathways, receptor-interacting protein 1 (RIP1), orchestrates a complex control of multiple responses and may link DR-associated signaling complexes to ROS production by mitochondria. Yet, RIP1 is also an important regulator of endogenous anti-oxidants and ROS scavenging enzymes, because it is required for nuclear factor kappaB activation that results in expression of anti-apoptotic and anti-oxidant proteins. Alteration of RIP1 function may result in ROS accumulation and abnormal c-Jun N-terminal protein kinase activation, affecting inflammatory responses, innate immunity, stress responses, and cell survival. These molecular mechanisms may be involved in neoplastic, autoimmune, neurodegenerative, inflammatory, and metabolic diseases.
Temkin
Vladislav
V
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Karin
Michael
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology; D003920:Diabetes Mellitus / Q000276:immunology; D006801:Humans; D007109:Immunity; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism*; D053218:Receptors, Death Domain / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000975:Antioxidants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D053218:Receptors, Death Domain; D014409:Tumor Necrosis Factor-alpha; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases