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组织蛋白酶 H:分子特征及功能和机制线索。

Cathepsin H: Molecular characteristics and clues to function and mechanism.

机构信息

Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.

Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China; Aerospace Medical Center, Aerospace Center Hospital, Beijing 100081, China.

出版信息

Biochem Pharmacol. 2023 Jun;212:115585. doi: 10.1016/j.bcp.2023.115585. Epub 2023 May 5.

Abstract

Cathepsin H (CatH) is a lysosomal cysteine protease with a unique aminopeptidase activity that is extensively expressed in the lung, pancreas, thymus, kidney, liver, skin, and brain. Owing to its specific enzymatic activity, CatH has critical effects on the regulation of biological behaviours of cancer cells and pathological processes in brain diseases. Moreover, a neutral pH level is optimal for CatH activity, so it is expected to be active in the extra-lysosomal and extracellular space. In the present review, we describe the expression, maturation, and enzymatic properties of CatH, and summarize the available experimental evidence that mechanistically links CatH to various physiological and pathological processes. Finally, we discuss the challenges and potentials of CatH inhibitors in CatH-induced disease therapy.

摘要

组织蛋白酶 H(CatH)是一种溶酶体半胱氨酸蛋白酶,具有独特的氨肽酶活性,广泛表达于肺、胰腺、胸腺、肾、肝、皮肤和脑等组织。由于其特有的酶学活性,CatH 对癌细胞的生物学行为和脑部疾病的病理过程的调控具有重要影响。此外,CatH 的最适活性 pH 值为中性,因此有望在溶酶体外和细胞外空间发挥作用。在本综述中,我们描述了 CatH 的表达、成熟和酶学特性,并总结了将 CatH 与各种生理和病理过程联系起来的现有实验证据。最后,我们讨论了 CatH 抑制剂在 CatH 诱导性疾病治疗中的挑战和潜力。

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