PTRH2: an adhesion regulated molecular switch at the nexus of life, death, and differentiation.
PTRH2: an adhesion regulated molecular switch at the nexus of life, death, and differentiation.
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DOI：
10.1038/s41420-020-00357-0
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发表时间：
2020-11-12
影响因子：
7
通讯作者：
Matter ML
中科院分区：
文献类型：
--
作者：
Corpuz AD;Ramos JW;Matter ML
肽基-tRNA水解酶2（PTRH 2; Bit-1; Bit 1）是粘附信号和Bcl 2表达的未被充分认识的调节剂。其在肌肉分化和整合素介导的信号传导中的关键作用是最近确定的由一组Ptrh 2基因突变引起的患者综合征的病理学的核心。这些功能丧失突变在骨骼肌、内分泌和神经系统表现出严重有害表型的患者中被鉴定，导致称为婴儿型多系统神经、内分泌和胰腺疾病（IMNEPD）的综合征。相比之下，在癌症中PTRH 2是促进恶性和转移的潜在致癌基因。PTRH 2除了调节Bcl 2表达之外还调节PI 3 K/AKT和ERK信号传导，从而调节响应于粘附的关键细胞过程，包括细胞存活、生长和分化。在这篇综述中，我们讨论了这一重要的细胞存活，失巢凋亡和分化调节剂的科学状况，以及进一步研究和翻译的机会。我们开始与PTRH 2的结构，调节和亚细胞定位的简要概述。我们讨论了迄今为止发现的导致发育迟缓和多系统疾病的基因突变簇。然后，我们讨论了PTRH 2和粘附在乳腺癌，肺癌和食管癌中的作用，重点是参与细胞存活，细胞生长和细胞分化的信号通路。
Peptidyl-tRNA hydrolase 2 (PTRH2; Bit-1; Bit1) is an underappreciated regulator of adhesion signals and Bcl2 expression. Its key roles in muscle differentiation and integrin-mediated signaling are central to the pathology of a recently identified patient syndrome caused by a cluster of Ptrh2 gene mutations. These loss-of-function mutations were identified in patients presenting with severe deleterious phenotypes of the skeletal muscle, endocrine, and nervous systems resulting in a syndrome called Infantile-onset Multisystem Nervous, Endocrine, and Pancreatic Disease (IMNEPD). In contrast, in cancer PTRH2 is a potential oncogene that promotes malignancy and metastasis. PTRH2 modulates PI3K/AKT and ERK signaling in addition to Bcl2 expression and thereby regulates key cellular processes in response to adhesion including cell survival, growth, and differentiation. In this Review, we discuss the state of the science on this important cell survival, anoikis and differentiation regulator, and opportunities for further investigation and translation. We begin with a brief overview of the structure, regulation, and subcellular localization of PTRH2. We discuss the cluster of gene mutations thus far identified which cause developmental delays and multisystem disease. We then discuss the role of PTRH2 and adhesion in breast, lung, and esophageal cancers focusing on signaling pathways involved in cell survival, cell growth, and cell differentiation.
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DOI：
10.1158/1541-7786.mcr-12-0144
发表时间：
2012-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
Liu, Hongtao
影响因子：
4.9
作者：
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通讯作者：
Megeney LA
影响因子：
37.3
作者：
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影响因子：
3.7
作者：
Bessette DC;Tilch E;Seidens T;Quinn MC;Wiegmans AP;Shi W;Cocciardi S;McCart-Reed A;Saunus JM;Simpson PT;Grimmond SM;Lakhani SR;Khanna KK;Waddell N;Al-Ejeh F;Chenevix-Trench G
通讯作者：
Chenevix-Trench G