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机构地区:[1]浙江师范大学化学与生命科学学院,金华321004
出 处:《生命的化学》2015年第3期365-370,共6页Chemistry of Life
基 金:国家自然科学基金项目(31101057;31470082);浙江省自然科学基金项目(LY14C120001)
摘 要:Caspase是一类胱天蛋白酶家族。大多数Caspase以半胱氨酸作为裂解底物的亲核基团,通过切割底物蛋白引起细胞凋亡。但是,研究发现Caspase存在非凋亡性作用,即Caspase活化后并不引发细胞凋亡,而是通过剪切不同底物或蛋白质互作,介导其他生物学事件,包括细胞增殖、分化、迁移、存活、形态重塑等。部分细胞的分化依赖于Caspase瞬时或位点局限的激活,细胞形态呈现类似于凋亡(不完全凋亡)的改变。Caspase对信号分子、转录因子的剪切灭活,可发挥转换细胞命运和分化进程的作用。在组织损伤时,应激细胞Caspase活化后,可提高自身防御能力,并通过旁分泌来指导邻近细胞进行补偿修复。因此,Caspase的活化不仅仅是一种细胞死亡信号,它的特定活化还是更改细胞形态、行为、命运的重要应激信号和效应分子。Caspases are a family of cysteine proteases. Most Caspases play a central role in activating cell apoptosis by cleaVing selected target substrates in a cysteine-dependent aspartate-directed manner. Addition- ally to their established function in apoptosis, growing evidences implicate that apoptotic Caspases also par- ticipate in several non-apoptotic cellular processes, including cell proliferation, differentiation, migration, sur- vival, and restructuring via cleaving target proteins or interacting with other proteins. In some cell types, their differentiation requires the transient or local activation of Caspases, and is morphologically viewed as a kind of incomplete apoptosis. The cleavage of signal molecules and transcriptional factors by Caspases, can switch cell fate and regulate differentiation process. In tissue injury, stressed cells can activate Caspases to enhance cell survival, and direct the compensatory proliferation of neighboring cells through paracrine mechanisms. Therefore, Caspases do not always execute cell apoptosis and, instead, might be important signal molecules and effectors for the control of cell morphology, behavior and fate determination.
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