TNFシグナリング・カスケードの解明

 Tumor necrosis factor (TNF) is a pleiotropic cytokine, which exerts multiple biological actions in different cell systems. In addition to induction of apoptotic cell death, TNF mediates cellular proliferation and differentiation. TNF is also involved in the pathogenesis of many diseases, such as cancer, sepsis, hemophagocytic syndrome, rheumatoid arthritis, inflammatory bowel disease, osteoporosis, atherosclerosis and diabetes.

 Signal of TNF is mediated via two distinct receptors with molecular weight of 55 kDa (TNF-R1) and 75 kDa (TNF-R2). The cytoplasmic tail of TNF-R1 contains a death domain (DD), which is essential for transduction of a death signal, while TNF-R2 does not have a DD motif. Ligation of TNF-R with TNF triggers various intracellular events, including recruitment of adaptor proteins, such as TNF receptor-associated death domain (TRADD), Fas-associated death domain (FADD), receptor-interacting protein (RIP) and TNF receptor-associated factor (TRAF), activation of caspase pathways and sphingomyelinase, generation of ceramide, activation of protein kinase C and nuclear factor kappa B (NF-κB), and down-regulation of c-myc proto-oncogene expression. These diverse signaling pathways may terminate in different cellular responses.

 We study the molecular mechanisms of the intracellular signaling pathway of TNF, specifically during TNF-mediated differentiation and apoptosis of leukemia cells. おおお

 

 
 

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