Dismantling the Apoptotic Cell
Dismantling the Apoptotic Cell
复制标题
拆除凋亡细胞
DOI：
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
S. Kornbluth
中科院分区：
文献类型：
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作者：
Paula B Deming;S. Kornbluth
细胞凋亡是一种细胞死亡的程序，由于细胞结构和功能通路的系统分解，导致死亡细胞的形态和生化上的巨大变化。执行凋亡程序的蛋白质是一组被称为半胱氨酸依赖的天冬氨酸特异性蛋白水解酶(Caspase)的蛋白。半胱氨酸天冬氨酸酶在天冬氨酸残基上对许多细胞底物进行蛋白水解性切割，这可能使它们在功能上处于不活跃状态，或者提供有助于促进细胞死亡的新活性。Caspase在细胞凋亡过程中靶向的底物包括参与维持细胞骨架和细胞器结构的各个方面的蛋白质，以及在细胞功能至关重要的信号网络中发挥作用的蛋白质。在细胞凋亡的执行阶段之后，细胞身体被有序地包装成被吞噬细胞感知的膜结合的凋亡体，吞噬细胞整齐地吞噬死亡的细胞，而不会引发免疫反应。
主要概念：
半胱氨酸半胱氨酸蛋白酶是一种半胱氨酸水解酶，受多种细胞外和细胞内刺激而被激活，随后通过系统地裂解细胞内蛋白来执行细胞死亡程序。
半胱氨酸天冬氨酸酶的激活存在一个层次，通过激活启动子半胱氨酸酶来裂解和激活效应型半胱氨酸酶，然后通过蛋白水解性的细胞内裂解来分解细胞。
与细胞凋亡相关的细胞形态变化包括三个阶段：释放、膜泡化和凝聚。
Caspase介导的靶蛋白切割可以产生稳定的功能效应片段或不稳定的片段，这些片段很快就会被降解。
Caspase针对细胞结构的多个方面，导致细胞器和细胞骨架的崩溃。
调节对细胞生存至关重要的细胞过程的信号网络被半胱氨酸天冬氨酸酶失活。
当死亡的细胞在凋亡过程中被分解时，它会通过在细胞表面显示‘吃我’的信号和释放‘找到我’的信号来协调自己的处置。
关键词：
引发剂caspase；
效应子caspase；
膜泡沫化；
核解体；
细胞凝聚；
凋亡小体
Apoptosis is a programme of cell death that results in dramatic morphological and biochemical changes in the dying cell due to the systematic dismantling of cellular architecture and functional pathways. The proteins that execute the apoptotic programme are a group of proteases termed caspases (cysteine-dependent aspartate-specific protease). Caspases proteolytically cleave a host of cellular substrates at aspartate residues, which may render them either functionally inactive or confer novel activities that help to promote cellular demise. Substrates targeted by caspases during the apoptotic programme include proteins involved in maintaining various aspects of cytoskeletal and organelle architecture as well as proteins that function in signalling networks critical for cell function. Following the execution phase of apoptosis, the cellular corpse is packaged in an orderly fashion into membrane-bound apoptotic bodies that are sensed by phagocytes, which neatly engulf the dead cell without eliciting an immune response.
Key concepts:
Apoptotic caspases are cysteine proteases which become activated in response to diverse extracellular and intracellular stimuli and subsequently carry out the cell death programme by systematically cleaving intracellular proteins.
A hierarchy of caspase activation exists whereby initiator caspases become activated to cleave and activate effector caspases, which then dismantle the cell through proteolytical cleavage of intracellular.
The cellular morphological changes associated with apoptosis encompass three stages: release, membrane blebbing and condensation.
Caspase-mediated cleavage of target proteins may produce stable functional effector fragments or unstable fragments that are quickly degraded.
Caspases target multiple aspects of the cellular architecture to induce collapse of organelles and the cytoskeleton.
Signalling networks that regulate cellular processes critical for cell survival are inactivated by caspases.
As the dying cell is dismantled during the apoptotic process, it orchestrates its own disposal by displaying ‘eat me’ signals on its cell surface and releasing ‘find me’ signals to recruit phagocytic cells.
Keywords:
initiator caspase;
effector caspase;
membrane blebbing;
nuclear disintegration;
cellular condensation;
apoptotic bodies