The Probable, Possible, and Novel Functions of ERp29.

The Probable, Possible, and Novel Functions of ERp29.
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DOI:
10.3389/fphys.2020.574339
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发表时间:
2020
影响因子:
4
通讯作者:
Rubenstein RC
Rubenstein RC
中科院分区:
医学2区
文献类型:
--
作者:
Brecker M;Khakhina S;Schubert TJ;Thompson Z;Rubenstein RC

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29 kDa的内质网(ER)蛋白(ERp29)是一种普遍表达的细胞因子,具有多种关键作用。ERp29调节多种跨膜和分泌蛋白的生物合成和运输,包括囊性纤维化跨膜传导调节剂(CFTR)、上皮钠通道(ENaC)、甲状腺球蛋白、连接蛋白43半通道和胰岛素原。假设ERp29通过与KDEL受体的相互作用,通过COP II机制促进ER向顺式高尔基货物蛋白转运;这种相互作用可能有助于将ERp29客户机加载到COP II囊泡中。ERp29也在内质网应激(ERS)和未折叠蛋白反应(UPR)中发挥作用,并与肿瘤发生有关。在这里,我们回顾了ERp29的大量客户,其作为高尔基护送蛋白的内质网的作用,并进一步提出ERp29作为蛋白质错误折叠和错误运输疾病相关治疗的潜在靶点。
The luminal endoplasmic reticulum (ER) protein of 29 kDa (ERp29) is a ubiquitously expressed cellular agent with multiple critical roles. ERp29 regulates the biosynthesis and trafficking of several transmembrane and secretory proteins, including the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial sodium channel (ENaC), thyroglobulin, connexin 43 hemichannels, and proinsulin. ERp29 is hypothesized to promote ER to cis-Golgi cargo protein transport via COP II machinery through its interactions with the KDEL receptor; this interaction may facilitate the loading of ERp29 clients into COP II vesicles. ERp29 also plays a role in ER stress (ERS) and the unfolded protein response (UPR) and is implicated in oncogenesis. Here, we review the vast array of ERp29’s clients, its role as an ER to Golgi escort protein, and further suggest ERp29 as a potential target for therapies related to diseases of protein misfolding and mistrafficking.
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