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首页> 外文期刊>Journal of Molecular Biology >Essential role of PACT-mediated PKR activation in tunicamycin-induced apoptosis.
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Essential role of PACT-mediated PKR activation in tunicamycin-induced apoptosis.

机译：PACT介导的PKR激活在衣霉素诱导的细胞凋亡中的重要作用。

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摘要

Cellular stresses such as disruption of calcium homeostasis, inhibition of protein glycosylation, and reduction of disulfide bonds result in accumulation of misfolded proteins in the endoplasmic reticulum (ER) and lead to cell death by apoptosis. Tunicamycin, which is an inhibitor of protein glycosylation, induces ER stress and apoptosis. In this study, we examined the involvement of double-stranded RNA (dsRNA)-activated protein kinase (PKR) and its protein activator PACT in tunicamycin-induced apoptosis. We demonstrate for the first time that PACT is phosphorylated in response to tunicamycin and is responsible for PKR activation by direct interaction. Furthermore, PACT-induced PKR activation is essential for tunicamycin-induced apoptosis, since PACT as well as PKR null cells are markedly resistant to tunicamycin and show defective eIF2alpha phosphorylation and C/EBP homologous protein (CHOP, also known as GADD153) induction especially at low concentrations of tunicamycin. Reconstitution of PKR and PACT expression in the null cells renders them sensitive to tunicamycin, thus demonstrating that PACT-induced PKR activation plays an essential function in induction of apoptosis.
机译：细胞应力，例如钙稳态的破坏，蛋白质糖基化的抑制和二硫键的减少，导致错误折叠的蛋白质积聚在内质网（ER）中，并通过凋亡导致细胞死亡。衣霉素是蛋白质糖基化的抑制剂，可诱导内质网应激和细胞凋亡。在这项研究中，我们检查了双链RNA（dsRNA）激活的蛋白激酶（PKR）及其蛋白激活剂PACT在衣霉素诱导的细胞凋亡中的作用。我们首次证明，PACT对衣霉素具有磷酸化作用，并通过直接相互作用负责PKR活化。此外，PACT诱导的PKR激活对于衣霉素诱导的细胞凋亡至关重要，因为PACT和PKR空细胞对衣霉素具有明显的耐药性，并且显示出有缺陷的eIF2alpha磷酸化和C / EBP同源蛋白（CHOP，也称为GADD153）诱导，特别是在低浓度的衣霉素。无效细胞中PKR和PACT表达的重建使它们对衣霉素敏感，因此证明PACT诱导的PKR激活在诱导细胞凋亡中起重要作用。

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