TRAP1 revisited: Novel localizations and functions of a 'next-generation' biomarker (Review)
TRAP1 revisited: Novel localizations and functions of a 'next-generation' biomarker (Review)
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DOI：
10.3892/ijo.2014.2530
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发表时间：
2014-09-01
影响因子：
5.2
通讯作者：
Esposito, Franca
中科院分区：
文献类型：
--
作者：
Amoroso, Maria Rosaria;Matassa, Danilo Swann;Esposito, Franca
在过去的十年中，涉及热休克蛋白TRAP 1/HSP 75在癌症和其他疾病中的新分子机制和途径的鉴定和表征增强了科学兴趣。最近的报道表明，TRAP 1在肿瘤转化的发生中处于多个关键过程的十字路口。事实上，TRAP 1：i）通过抑制琥珀酸脱氢酶（线粒体呼吸链的复合物II）有助于肿瘤向有氧糖酵解的转变; ii）是促存活信号传导途径的一部分，旨在逃避氧化剂和抗癌药物的毒性作用，并通过减少ROS产生保护线粒体免受破坏性刺激; iii）通过直接参与调节蛋白质合成和蛋白质共翻译降解来控制蛋白质稳态。因此，TRAP 1似乎是在肿瘤转化过程中不同代谢过程的交叉点具有平衡功能的中心调节蛋白。因此，它可以被认为是一个有吸引力的目标，同时开发新的抗癌策略和一个有前途的研究模型，以了解肿瘤细胞的生物学在系统水平。本文综述了TRAP 1生物学的最新进展，并提出了一个新的全面的看法，其功能。
In the last decade, the identification and characterization of novel molecular mechanisms and pathways involving the heat shock protein TRAP1/HSP75 in cancers and other diseases enhanced the scientific interest. Recent reports have shown that TRAP1 stays at the crossroad of multiple crucial processes in the onset of neoplastic transformation. In fact, TRAP1: i) contributes to the tumor's switch to aerobic glycolysis through the inhibition of succinate dehydrogenase, the complex II of the mitochondrial respiratory chain; ii) is part of a pro-survival signaling pathway aimed at evading the toxic effects of oxidants and anticancer drugs and protects mitochondria against damaging stimuli via a decrease of ROS generation; iii) controls protein homeostasis through a direct involvement in the regulation of protein synthesis and protein co-translational degradation. Therefore, TRAP1 seems to be a central regulatory protein with balancing functions at the intersection of different metabolic processes during the neoplastic transformation. For this reason, it can be considered at the same time an attractive target for the development of novel anticancer strategies and a promising study model to understand the biology of tumor cells at a systemic level. This review summarizes the most recent advances in TRAP1 biology and proposes a new comprehensive view of its functions.