Ubiquitin-proteasome pathway in the pathogenesis of liver disease
Ubiquitin-proteasome pathway in the pathogenesis of liver disease
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DOI：
10.1007/3-540-27194-5_32
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Bardag-Gorce, F
中科院分区：
文献类型：
--
作者：
French, SW;Bardag-Gorce, F
泛素-蛋白酶体途径作为所有细胞内蛋白质消化的调节系统的发现，使人们认识到蛋白质周转控制的重要性。这种控制是一种调节细胞过程和细胞内蛋白质质量控制的机制。许多肝细胞功能是由这种蛋白质降解机制调节的。这些包括细胞周期检查点和转录因子的激活，如核因子-κB (NF-κB)（第29章）和缺氧诱导因子-1α (HIF-1α)（第26章）[28,67,71]。蛋白酶体的缺失或泛素-蛋白酶体通路的抑制可导致肝细胞损伤，包括增殖和凋亡[74,107]，以及聚集的细胞角蛋白[24]的肝包涵体。肝细胞基因表达依赖于蛋白酶体的转录因子激活，可以抑制肝脏的炎症反应和对缺氧损伤的反应。本文综述了泛素-蛋白酶体途径在肝损伤稳态机制中的重要性。
The discovery of the ubiquitin-proteasome pathway as a regulated system of protein digestion within all cells [32] has led to an appreciation of the importance of protein turnover control. This control is a mechanism for regulation of cellular processes and quality control of intracellular proteins. Many liver cell functions are regulated by this mechanism of protein degradation. These include cell cycle check points and activation of transcription factors such as nuclear factor-κB (NF-κB)(Chapter 29), and hypoxia inducible factor-1α (HIF-1α)(Chapter 26)[28, 67, 71]. The loss of proteasomes or the inhibition of the ubiquitin-proteasome pathway can lead to hepatocellular injury including proliferation and apoptosis [74, 107], and hepatic inclusions of aggregated cytokeratins [24]. Liver cell gene expressions, dependent on transcription factor activation by the proteasome, could impede the inflammatory response of the liver and the response to hypoxic injury. The importance of the ubiquitin-proteasome pathway to the homeostatic mechanisms involved in liver injury is the focus of this review.