Regulation of p53 and Cancer Signaling by Heat Shock Protein 40/J-Domain Protein Family Members.
Regulation of p53 and Cancer Signaling by Heat Shock Protein 40/J-Domain Protein Family Members.
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热休克蛋白40/J结构域蛋白家族成员对p53和癌症信号的调节
DOI：
10.3390/ijms222413527
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发表时间：
2021-12-16
影响因子：
5.6
通讯作者：
Iwakuma T
中科院分区：
文献类型：
--
作者：
Kaida A;Iwakuma T
热休克蛋白（HSPs）是一种分子伴侣蛋白，可协助多种细胞活动，包括蛋白质折叠、细胞内运输、蛋白质复合物的组装或拆卸，以及错误折叠或聚集蛋白质的稳定或降解。HSP40，也被称为J结构域蛋白（jdp），是最大的家族，有超过50个成员，包含高度保守的J结构域，负责与HSP70结合并作为共伴侣刺激atp酶活性。肿瘤抑制因子p53 （p53）是人类癌症中最常见的突变基因，是与HSP40/ jdp功能相互作用的蛋白之一。大多数p53突变是错义突变，除了失去肿瘤抑制功能外，还会获得意想不到的致癌活性，称为功能获得（gain of function， GOF）。此外，野生型p53 （wtp53）和突变型p53 （mutp53）的稳定性和水平分别对其抑瘤和致癌活性至关重要。然而，wtp53和mutp53的调控机制尚不完全清楚。越来越多的报告表明HSP40/ jdp对wtp53和mutp53水平和/或活性有调节作用。在此，我们总结了有关HSP40/ jdp与p53和癌症信号联系的最新知识，以提高我们对肿瘤抑制wtp53和致癌mutp53 GOF活性调控的理解。
Heat shock proteins (HSPs) are molecular chaperones that assist diverse cellular activities including protein folding, intracellular transportation, assembly or disassembly of protein complexes, and stabilization or degradation of misfolded or aggregated proteins. HSP40, also known as J-domain proteins (JDPs), is the largest family with over fifty members and contains highly conserved J domains responsible for binding to HSP70 and stimulation of the ATPase activity as a co-chaperone. Tumor suppressor p53 (p53), the most frequently mutated gene in human cancers, is one of the proteins that functionally interact with HSP40/JDPs. The majority of p53 mutations are missense mutations, resulting in acquirement of unexpected oncogenic activities, referred to as gain of function (GOF), in addition to loss of the tumor suppressive function. Moreover, stability and levels of wild-type p53 (wtp53) and mutant p53 (mutp53) are crucial for their tumor suppressive and oncogenic activities, respectively. However, the regulatory mechanisms of wtp53 and mutp53 are not fully understood. Accumulating reports demonstrate regulation of wtp53 and mutp53 levels and/or activities by HSP40/JDPs. Here, we summarize updated knowledge related to the link of HSP40/JDPs with p53 and cancer signaling to improve our understanding of the regulation of tumor suppressive wtp53 and oncogenic mutp53 GOF activities.
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