Sheikh M Saeed, Huang Ying
Department of Pharmacology, State University of New York, Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
Curr Cancer Drug Targets. 2004 Feb;4(1):97-104. doi: 10.2174/1568009043481597.
To date six bona fide death receptors (DRs) have been discovered and include tumor necrosis factor receptor 1 (TNF-R1), Fas, DR3, DR4, DR5 and DR6. Each receptor contains an extracellular region and an intracellular region; the intracellular region harbors a death domain that is critical for transduction of apoptotic signals. These death receptors are activated by their respective ligands. For example, TNFalpha activates TNF-R1 while FasL and TL1A activate Fas and DR3 respectively. TNF-related apoptosis inducing ligand (TRAIL), also known as Apo2L, activates DR4 and DR5. The ligand for DR6 has yet to be identified. These death receptors are also believed to be activated in a ligand-independent manner. A large body of recent evidence suggests that death receptors could be utilized as key molecular targets to develop novel therapeutics. This review discusses the pros and cons of targeting death receptors in the development of novel cancer therapeutic agents.
迄今为止，已发现六种真正的死亡受体（DRs），包括肿瘤坏死因子受体1（TNF-R1）、Fas、DR3、DR4、DR5和DR6。每个受体都包含一个细胞外区域和一个细胞内区域；细胞内区域含有一个死亡结构域，这对于凋亡信号的转导至关重要。这些死亡受体被其各自的配体激活。例如，TNFα激活TNF-R1，而FasL和TL1A分别激活Fas和DR3。肿瘤坏死因子相关凋亡诱导配体（TRAIL），也称为Apo2L，激活DR4和DR5。DR6的配体尚未确定。这些死亡受体也被认为可以以不依赖配体的方式被激活。最近大量证据表明，死亡受体可作为开发新型治疗药物的关键分子靶点。本综述讨论了在新型癌症治疗药物开发中靶向死亡受体的利弊。
