Bredesen D E, Mehlen P, Rabizadeh S
The Buck Institute for Age Research, Novato, CA 94945, USA.
Cell Death Differ. 2005 Aug;12(8):1031-43. doi: 10.1038/sj.cdd.4401680.
Cells depend for their survival on stimulation by trophic factors and other prosurvival signals, the withdrawal of which induces apoptosis, both via the loss of antiapoptotic signaling and the activation of proapoptotic signaling via specific receptors. These receptors, dubbed dependence receptors, activate apoptotic pathways following the withdrawal of trophic factors and other supportive stimuli. Such receptors may feature in developmental cell death, carcinogenesis (including metastasis), neurodegeneration, and possibly subapoptotic events such as neurite retraction and somal atrophy. Mechanistic studies of dependence receptors suggest that these receptors form ligand-dependent complexes that include specific caspases. Complex formation in the absence of ligand leads to caspase activation by a mechanism that is typically dependent on caspase cleavage of the receptor itself, releasing proapoptotic peptides. Cellular dependence receptors, considered in the aggregate, may thus form a system of molecular integration, analogous to the electrical integration system provided by dendritic arbors in the nervous system.
细胞的存活依赖于营养因子和其他促存活信号的刺激，这些信号的撤除会诱导细胞凋亡，其途径包括抗凋亡信号的丧失以及通过特定受体激活促凋亡信号。这些受体被称为依赖受体，在营养因子和其他支持性刺激撤除后会激活凋亡途径。此类受体可能参与发育性细胞死亡、致癌作用（包括转移）、神经退行性变，以及可能参与诸如神经突回缩和胞体萎缩等亚凋亡事件。对依赖受体的机制研究表明，这些受体形成依赖配体的复合物，其中包括特定的半胱天冬酶。在没有配体的情况下形成复合物会通过一种通常依赖于受体自身半胱天冬酶切割的机制导致半胱天冬酶激活，从而释放促凋亡肽。因此，总体而言，细胞依赖受体可能形成一个分子整合系统，类似于神经系统中树突分支提供的电整合系统。
