期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 276, 期 24, 页码 21907-21915出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M011565200
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Mammalian caspases are a family of cysteine proteases that plays a critical role in apoptosis, We have analyzed caspase-2 processing in human cell lines containing defined mutations in caspase-3 and caspase-9, Here we demonstrate that caspase-2 processing, during cell death induced by UV irradiation, depends both on caspase-9 and caspase-3 activity, while, during TNF-alpha -dependent apoptosis, capase-2 processing is independent of caspase-9 but still requires caspase-3, In vitro procaspase-2 is the preferred caspase cleaved by caspase-3, while caspase-7 cleaves procaspase-2 with reduced efficiency. We have also demonstrated that caspase-2-mediated apoptosis requires caspase-9 and that cells co-expressing caspase-2 and a dominant negative form of caspase-9 are impaired in activating a normal apoptotic response and release cytochrome c into the cytoplasm, Our findings suggest a role played by caspase-2 as a regulator of the mitochondrial integrity and open questions on the mechanisms responsible for its activation during cell death.
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