Cathepsin H: Molecular characteristics and clues to function and mechanism

Yanfeng Wang; Juan Zhao; Yebo Gu; Haiping Wang; Muzhou Jiang; Shuxuan Zhao; Hong Qing; Junjun Ni

doi:10.1016/j.bcp.2023.115585

Cathepsin H: Molecular characteristics and clues to function and mechanism

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

Authors

Yanfeng Wang¹, Juan Zhao², Yebo Gu³, Haiping Wang⁴, Muzhou Jiang⁵, Shuxuan Zhao¹, Hong Qing⁶, Junjun Ni⁷

Affiliations

¹ Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China.
² 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.
³ Department of Stomatology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.
⁴ School of Pharmaceutical Science, Nanjing Tech University, Nanjing, China.
⁵ Department of Periodontics, Liaoning Provincial Key Laboratory of Oral Diseases, School and Hospital of Stomatology, China Medical University, Shenyang 110002, China.
⁶ Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China. Electronic address: hqing@bit.edu.cn.
⁷ Key Laboratory of Molecular Medicine and Biotherapy, Department of Biology, School of Life Science, Beijing Institute of Technology, Beijing 100081, China. Electronic address: nijunjun@bit.edu.cn.

PMID: 37148981
DOI: 10.1016/j.bcp.2023.115585

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.

Keywords: Cathepsin H; Inhibitor; Pathophysiology; Protease maturation; Protease substrate.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Cathepsin D* / chemistry
Cathepsin D* / metabolism
Cathepsin H
Humans
Lung* / metabolism

Substances

Cathepsin D
Cathepsin H
CTSH protein, human