Activation of PERK kinase in neural cells by proteasome inhibitor treatment.
Activation of PERK kinase in neural cells by proteasome inhibitor treatment.
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DOI：
10.1111/j.1471-4159.2009.06448.x
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发表时间：
2010-01
影响因子：
4.7
通讯作者：
Keller JN
中科院分区：
文献类型：
--
作者：
Zhang L;Ebenezer PJ;Dasuri K;Bruce-Keller AJ;Fernandez-Kim SO;Liu Y;Keller JN
蛋白酶体蛋白水解途径的抑制是正常衰老以及各种神经退行性疾病的结果，并且被认为通过不同的机制在每种情况下促进细胞毒性。在本研究中，我们检查了蛋白酶体抑制是否会改变蛋白激酶 (PKR) 样 ER 激酶 (PERK)。我们的研究表明，蛋白酶体抑制剂可诱导原代大鼠神经元以及 N2a 神经细胞系中 PERK 的瞬时激活。 PERK 的 siRNA 实验表明，PERK 的调节与调节毒性、泛素化蛋白水平或响应蛋白酶体抑制剂治疗的核糖体扰动没有显着关系。令人惊讶的是，观察到 PERK 参与蛋白酶体抑制剂治疗后 p38 激酶的上调。总而言之，这些数据证明了蛋白酶体抑制激活 PERK 的能力，并证明了蛋白酶体抑制后 PERK 与神经细胞中 p38 激酶激活之间的新交互作用。总而言之，这些数据对于理解蛋白酶体抑制改变神经稳态的基础以及蛋白酶体抑制调节细胞信号级联的基础具有重要意义。
Inhibition of the proteasome proteolytic pathway occurs as the result of normal aging, as well as in a variety of neurodegenerative conditions, and is believed to promote cellular toxicity in each of these conditions through diverse mechanisms. In the present study we examined whether proteasome inhibition alters the protein kinase (PKR)-like ER kinase (PERK). Our studies demonstrate that proteasome inhibitors induce the transient activation of PERK in both primary rat neurons as well as the N2a neural cell line. Experiments with siRNA to PERK demonstrated that the modulation of PERK was not significant involved in regulating toxicity, ubiquitinated protein levels, or ribosome perturbations in response to proteasome inhibitor treatment. Surprisingly, PERK was observed to be involved in the upregulation of p38 kinase following proteasome inhibitor treatment. Taken together, these data demonstrate the ability of proteasome inhibition to activate PERK and demonstrate evidence for novel cross talk between PERK and the activation of p38 kinase in neural cells following proteasome inhibition. Taken together, these data have implications for understanding the basis by which proteasome inhibition alters neural homeostasis, and the basis by which cell signaling cascades are regulated by proteasome inhibition.
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影响因子：
16
作者：
Harding, HP;Zhang, YH;Ron, D
通讯作者：
Ron, D
影响因子：
2.4
作者：
Adams, J;Kauffman, M
通讯作者：
Kauffman, M
DOI：
10.1101/sqb.2001.66.499
发表时间：
2001-01-01
期刊：
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY
影响因子：
--
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
4.7
作者：
Keller, JN;Hanni, KB;Markesbery, WR
通讯作者：
Markesbery, WR