A caspase cleavage fragment of p115 induces fragmentation of the Golgi apparatus and apoptosis.

A caspase cleavage fragment of p115 induces fragmentation of the Golgi apparatus and apoptosis.
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DOI:
10.1083/jcb.200208013
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发表时间:
2002-11-25
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Shields D
Shields D
中科院分区:
其他
文献类型:
--
作者:
Chiu R;Novikov L;Mukherjee S;Shields D

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在哺乳动物细胞中,高尔基体在凋亡期间经历广泛的碎裂。p115是维持高尔基体结构组织所需的关键囊泡束缚蛋白。在这里,我们表明,p115被切割凋亡过程中的半胱天冬酶3和8。与表达天然p115的对照细胞相比,表达抗切割形式的p115的细胞在凋亡过程中延迟高尔基体碎裂。编码全长或p115的NH 2-末端半胱天冬酶切割片段的cDNA的表达对高尔基体形态没有影响。与此相反,COOH-末端caspase裂解产物p115本身的表达引起高尔基体片段化。此外,该片段易位到细胞核,其表达足以诱导细胞凋亡。最重要的是,在体内表达的COOH-末端片段的存在下,半胱天冬酶抑制剂,或与抗切割突变体的p115共表达后,显示p115降解发挥了关键作用,独立于高尔基体片段放大的凋亡反应。
In mammalian cells, the Golgi apparatus undergoes extensive fragmentation during apoptosis. p115 is a key vesicle tethering protein required for maintaining the structural organization of the Golgi apparatus. Here, we demonstrate that p115 was cleaved during apoptosis by caspases 3 and 8. Compared with control cells expressing native p115, those expressing a cleavage-resistant form of p115 delayed Golgi fragmentation during apoptosis. Expression of cDNAs encoding full-length or an NH2-terminal caspase cleavage fragment of p115 had no effect on Golgi morphology. In contrast, expression of the COOH-terminal caspase cleavage product of p115 itself caused Golgi fragmentation. Furthermore, this fragment translocated to the nucleus and its expression was sufficient to induce apoptosis. Most significantly, in vivo expression of the COOH-terminal fragment in the presence of caspase inhibitors, or upon coexpression with a cleavage-resistant mutant of p115, showed that p115 degradation plays a key role in amplifying the apoptotic response independently of Golgi fragmentation.
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