Cellular Mechanisms Controlling Caspase Activation and Function
Cellular Mechanisms Controlling Caspase Activation and Function
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DOI：
10.1101/cshperspect.a008672
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发表时间：
2013-06-01
影响因子：
7.2
通讯作者：
Kornbluth, Sally
中科院分区：
文献类型：
--
作者：
Parrish, Amanda B.;Freel, Christopher D.;Kornbluth, Sally
半胱天冬酶是凋亡性细胞死亡的主要驱动因素，切割对分解垂死细胞至关重要的细胞蛋白。半胱天冬酶最初被翻译为无活性的酶原前体，响应于多种细胞死亡刺激而被激活。除了其直接激活所需的因素（例如，二聚化衔接蛋白（在位于凋亡信号级联的顶点的起始物半胱天冬酶的情况下），半胱天冬酶在无数生理和病理环境中受多种细胞因子调节。例如，半胱天冬酶可以在后修饰（例如，通过磷酸化或泛素化）或通过调节因子与半胱天冬酶的酶原或活性形式的相互作用，改变其活化和/或活性。这些调节事件可抑制或增强酶活性或可影响对特定细胞底物的活性。最后，有新的文献表明，半胱天冬酶可以参与各种细胞过程无关的凋亡细胞死亡。在这些情况下，特别重要的是，半胱天冬酶保持在严格的控制下，以避免意外的细胞死亡。这是可能的，继续检查这些过程将揭示新的机制，半胱天冬酶的调控远远超出了控制凋亡细胞死亡的影响。
Caspases are the primary drivers of apoptotic cell death, cleaving cellular proteins that are critical for dismantling the dying cell. Initially translated as inactive zymogenic precursors, caspases are activated in response to a variety of cell death stimuli. In addition to factors required for their direct activation (e.g., dimerizing adaptor proteins in the case of initiator caspases that lie at the apex of apoptotic signaling cascades), caspases are regulated by a variety of cellular factors in a myriad of physiological and pathological settings. For example, caspases may be modified posttranslationally (e.g., by phosphorylation or ubiquitylation) or through interaction of modulatory factors with either the zymogenic or active form of a caspase, altering its activation and/or activity. These regulatory events may inhibit or enhance enzymatic activity or may affect activity toward particular cellular substrates. Finally, there is emerging literature to suggest that caspases can participate in a variety of cellular processes unrelated to apoptotic cell death. In these settings, it is particularly important that caspases are maintained under stringent control to avoid inadvertent cell death. It is likely that continued examination of these processes will reveal new mechanisms of caspase regulation with implications well beyond control of apoptotic cell death.