TNF receptor superfamily-induced cell death: redox-dependent execution.
Tumor necrosis factor (TNF) superfamily is a group of cytokines with important functions in immunity, inflammation, differentiation, control of cell proliferation, and apoptosis. TNFalpha is the founding member of the 19 different proteins that have so far been identified within this family. TNF family members exert their biological effects through the TNF receptor (TNFR) superfamily of cell surface receptors that share a stretch of approximately 80 amino acids within their cytoplasmic region, the death domain (DD), critical for recruiting the death machinery. Work over the last decade has unraveled critical signaling networks involved in TNFR-induced cell death, specifically using the constitutively expressed TNFR1 as a prototype. Of particular interest is the intermediary role of intracellular reactive oxygen species (ROS) in signal transduction after ligation of the TNFR1. With the increasing understanding of the of death receptor signaling pathways, the exact role of ROS in TNFalpha-induced execution is now believed to be far more complicated than originally thought. Recently, some important discoveries have underscored the critical role of ROS in TNFalpha signaling, notably in TNFalpha-mediated activation of nuclear factor-kappaB (NF-kappaB) and c-Jun N-terminal kinase (c-Jun NH2-terminal kinase, JNK), as well as in cell death (apoptotic and necrotic) pathways. Here we attempt to review the existing knowledge on the involvement of ROS in death receptor signaling using TNFalpha-TNFR1 as the model system, specifically addressing the involvement of intracellular ROS in TNFalpha-induced cell death and in TNFalpha-induced activation of NF-kappaB and JNK and their crosstalk.
Shen
Han-Ming
HM
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Bldg. MD9, Level 3, Singapore 117597, Singapore.
Pervaiz
Shazib
S
D000818:Animals; D017209:Apoptosis; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000502:physiology
D017382:Reactive Oxygen Species; D018124:Receptors, Tumor Necrosis Factor; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins