热疗中JNK信号通路的主导作用。

JNK signaling dominance in hyperthermia.

作者信息

Enomoto Atsushi, Fukasawa Takemichi

机构信息

Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

Department of Dermatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.

出版信息

Cell Stress Chaperones. 2025 May 6;30(4):100080. doi: 10.1016/j.cstres.2025.100080.

DOI:10.1016/j.cstres.2025.100080

PMID:40339685

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12145754/

Abstract

Hyperthermia is a promising anticancer treatment that induces heat stress, stimulating various signal transduction pathways to maintain cellular homeostasis. Mitogen-activated protein kinases (MAPKs) link various extracellular stimuli with cytoplasmic and nuclear mediators through a three-tiered cascade of kinases, including MAPKs, MAP2Ks, and MAP3Ks. In mammals, three major groups of MAPKs have been characterized: extracellular signal-regulated protein kinases (ERK), p38 MAPKs, and c-Jun NH-terminal kinases (JNK). Each group of MAPKs is heat-activated and exhibits distinct biological functions. However, the differences and advantages of the regulation of each MAPK with temperature changes remain unknown. Our results demonstrated that JNK was activated in a temperature-dependent manner, with degradation of the JNK phosphatases despite transient phosphorylation of ERK with induction of the ERK phosphatases. This brief insight deepens our current understanding of the deregulation of the ERK and JNK cascades in hyperthermia.

摘要

热疗是一种很有前景的抗癌治疗方法，它会引发热应激，刺激各种信号转导通路以维持细胞内稳态。丝裂原活化蛋白激酶（MAPK）通过包括MAPK、MAP2K和MAP3K在内的三级激酶级联反应，将各种细胞外刺激与细胞质和核介质联系起来。在哺乳动物中，已鉴定出三大类MAPK：细胞外信号调节蛋白激酶（ERK）、p38 MAPK和c-Jun氨基末端激酶（JNK）。每一类MAPK都可被热激活，并表现出不同的生物学功能。然而，随着温度变化，每种MAPK调节的差异和优势仍不明确。我们的结果表明，JNK以温度依赖性方式被激活，JNK磷酸酶降解，而ERK磷酸酶诱导时ERK会短暂磷酸化。这一简要见解加深了我们目前对热疗中ERK和JNK级联反应失调的理解。