PETCM 是 caspase-3 的激活剂，并以细胞色素 c (细胞 c) 依赖性方式发挥作用。 PETCM 促进 Apaf-1 寡聚化并诱导 HeLa 细胞中的细胞凋亡。
PETCM is an activator of caspase-3 [1].
Caspase-3 is a member of the cysteine-aspartic acid protease family and interacts with caspase-8 and caspase-9. Sequential activation of caspases plays an important role in cell apoptosis.
In HeLa S-100 cell cytosol, PETCM activated caspase-3 in a dose-dependent way and induced apoptosome formation. PETCM (0.2 mM) caused Apaf-1 shifted to a size of ~1 million daltons, which indicating apoptosome formation. Also, PETCM function required dATP. The activation effect of PETCM on caspase-3 was independent of PHAP proteins. When inhibited the activation activity of the PHAP proteins, PETCM reversed the suppression. When added to Q30 (Apaf-1/procaspase-9) plus cytochrome c and 10 μM dATP, recombinant PHAPI activated caspase-3. The activity was inhibited by recombinant ProT. While, PETCM reversed the inhibitory effect of ProT. PHAPI didn’t affect apoptosome formation and activated caspase-9 and Apaf-1, which were associated with apoptosome. ProT efficiently blocked formation of apoptosome and PETCM relieved this effect [1].
Reference:
[1].? Jiang X, Kim HE, Shu H, et al. Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway. Science, 2003, 299(5604): 223-226.
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