期刊
LEUKEMIA
卷 15, 期 7, 页码 1022-1032出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.leu.2402169
关键词
apoptosis; toxicity; signaling; TNF; CD95/Fas; TRAIL
Death receptors and their ligands exert important regulatory functions in the maintenance of tissue homeostasis and the physiological regulation of programmed cell death. Currently, six different death receptors are known including tumor necrosis factor (TNF) receptor-1, CD95 (Fas/APO-1), TNF receptor-related apoptosis-mediating protein (TRAMP), TNF-related apoptosis-inducing ligand (TRAIL) receptor-1 and -2, and death receptor-6 (DR6). The signaling pathways by which these receptors induce apoptosis are similar and rely on oligomerization of the receptor by death ligand binding, recruitment of an adapter protein through hemophilic interaction of cytoplasmic domains, and subsequent activation of an inducer caspase which initiates execution of the cell death programme. The ability of these receptors and their ligands to kill malignant cells was discovered early and helped to coin the term 'tumor necrosis factor' for the first identified death ligand. This review summarizes the current and rapidly expanding knowledge about the signaling pathways triggered by death receptor/ligand systems, their potency in experimental cancer therapy, and their therapeutic limitations, especially regarding their toxicity for non-malignant cells.
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