From death receptor to reactive oxygen species and c-Jun N-terminal protein kinase: the receptor-interacting protein 1 odyssey
- Immunol Rev. 2007 Dec;220:8-21. doi: 10.1111/j.1600-065X.2007.00560.x.
- 1. Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, La Jolla, CA, USA.
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.