p62/SQSTM1——兼具抗氧化应激作用与促肝癌作用的“杰ekyll博士与海德先生”。 （注：这里“杰ekyll博士与海德先生”是用文学形象比喻p62/SQSTM1具有两种不同甚至相反特性的复杂情况 ）
p62/SQSTM1-Dr. Jekyll and Mr. Hyde that prevents oxidative stress but promotes liver cancer.
作者信息
Taniguchi Koji, Yamachika Shinichiro, He Feng, Karin Michael
机构信息
Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, University of California San Diego, La Jolla, CA, USA.
Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
出版信息
FEBS Lett. 2016 Aug;590(15):2375-97. doi: 10.1002/1873-3468.12301. Epub 2016 Aug 6.
p62/SQSTM1 is a multifunctional signaling hub and autophagy adaptor with many binding partners, which allow it to activate mTORC1-dependent nutrient sensing, NF-κB-mediated inflammatory responses, and the NRF2-activated antioxidant defense. p62 recognizes polyubiquitin chains via its C-terminal domain and binds to LC3 via its LIR motif, thereby promoting the autophagic degradation of ubiquitinated cargos. p62 accumulates in many human liver diseases, including nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC), where it is a component of Mallory-Denk bodies and intracellular hyaline bodies. Chronic p62 elevation contributes to HCC development by preventing oncogene-induced senescence and death of cancer-initiating cells and enhancing their proliferation. In this review, we discuss p62-mediated signaling pathways and their roles in liver pathophysiology, especially NASH and HCC.
p62/SQSTM1是一个多功能信号枢纽和自噬衔接蛋白，有许多结合伴侣，使其能够激活mTORC1依赖性营养感知、NF-κB介导的炎症反应以及NRF2激活的抗氧化防御。p62通过其C末端结构域识别多聚泛素链，并通过其LIR基序与LC3结合，从而促进泛素化货物的自噬降解。p62在许多人类肝脏疾病中积累，包括非酒精性脂肪性肝炎（NASH）和肝细胞癌（HCC），它是马洛里-丹克小体和细胞内透明小体的组成部分。长期p62升高通过防止癌基因诱导的衰老和癌症起始细胞死亡并增强其增殖，促进HCC的发展。在这篇综述中，我们讨论了p62介导的信号通路及其在肝脏病理生理学中的作用，尤其是在NASH和HCC中的作用。
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