Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis.
Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis.
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DOI：
10.1084/jem.184.6.2399
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发表时间：
1996-12-01
期刊：
影响因子：
--
通讯作者：
Kufe D
中科院分区：
文献类型：
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作者：
Ghayur T;Hugunin M;Talanian RV;Ratnofsky S;Quinlan C;Emoto Y;Pandey P;Datta R;Huang Y;Kharbanda S;Allen H;Kamen R;Wong W;Kufe D
最近的研究表明，蛋白激酶C（PKC）δ在DNA损伤剂、肿瘤坏死因子和抗Fas抗体诱导的细胞凋亡开始时被蛋白水解激活。然而，PKCδ裂解与诱导凋亡的关系尚不清楚。目前的研究表明，全长PKCδ在DMQD 330 N处被半胱氨酸蛋白酶CPP32切割成催化活性片段。结果还表明，催化激酶片段在细胞中的过表达与染色质浓缩、核碎裂、亚G1期DNA的诱导和致死性相关。相比之下，全长PKCδ或激酶失活的PKCδ片段的过表达没有可检测的影响。研究结果表明，通过CPP32样蛋白酶对PKCδ的蛋白水解激活有助于与凋亡相关的表型变化。
Recent studies have shown that protein kinase C (PKC) δ is proteolytically activated at the onset of apoptosis induced by DNA-damaging agents, tumor necrosis factor, and anti-Fas antibody. However, the relationship of PKCδ cleavage to induction of apoptosis is unknown. The present studies demonstrate that full-length PKCδ is cleaved at DMQD330N to a catalytically active fragment by the cysteine protease CPP32. The results also demonstrate that overexpression of the catalytic kinase fragment in cells is associated with chromatin condensation, nuclear fragmentation, induction of sub-G1 phase DNA and lethality. By contrast, overexpression of full-length PKCδ or a kinase inactive PKCδ fragment had no detectable effect. The findings suggest that proteolytic activation of PKCδ by a CPP32-like protease contributes to phenotypic changes associated with apoptosis.