Identification and characterization of endoplasmic reticulum-associated protein, ERp43

Identification and characterization of endoplasmic reticulum-associated protein, ERp43
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DOI:
10.1016/j.gene.2006.06.030
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发表时间:
2007-01-15
期刊:
影响因子:
3.5
通讯作者:
Inone, Masayasu
Inone, Masayasu
中科院分区:
生物学3区
文献类型:
--
作者:
Nishikawa, Manabu;Kira, Yukimi;Inone, Masayasu

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从内质网(ER)腔中处理错误折叠的蛋白质是蛋白质分泌途径中存在的质量控制机制之一。通过ER相关的降解,错误折叠的底物被靶向细胞溶质,在那里它们被蛋白酶体降解。在这里,我们描述了一个人ER相关的43-kD蛋白(ERp 43)的减抑制杂交cDNA文库从ER应激处理的细胞测序的鉴定。ERp 43基因编码383个氨基酸残基的蛋白质,其含有潜在的跨膜结构域。分析表明,ERp 43主要位于ER。定量逆转录-聚合酶链反应表明,基因表达相对较高的神经元组织和肾脏中,与ERp 43蛋白在脊髓和肾脏中高度表达。在培养的细胞中,ERp 43的过表达加速细胞生长并抑制ER应激诱导的细胞死亡,而ERp 43表达的下调降低增殖率并增强这种类型的细胞死亡。这些发现表明ERp 43在细胞生长和ER应激诱导的细胞死亡中起重要作用。(c)2006 Elsevier B. V.保留所有权利。
Disposal of misfolded proteins from the lumen of the endoplasmic reticulum (ER) is one of the quality control mechanisms present in the protein secretory pathway. Through ER-associated degradation, misfolded substrates are targeted to the cytosol where they are degraded by proteasomes. Here we describe the identification of a human ER-associated 43-kD protein (ERp43) by sequencing of the subtraction suppression hybridization eDNA library from ER stress-treated cells. The ERp43 gene encodes a protein of 383 amino acid residues that contains a potential transmembrane domain. Analysis revealed that ERp43 is primarily located in the ER. Quantitative reverse transcriptase-polymerase chain reaction demonstrated that gene expression was relatively high in the neuronal tissues and in the kidney, with ERp43 protein highly expressed in the spinal cord and in the kidney. In cultured cells, overexpression of ERp43 accelerated cell growth and inhibited ER stress-induced cell death, while down-regulation of ERp43 expression decreased proliferation rate and enhanced this type of cell death. These findings indicate that ERp43 plays important roles in cell growth and ER stress-induced cell death. (c) 2006 Elsevier B.V. All rights reserved.