Cathepsin B

Related Reading

Cathepsin is a type of protease found in the cells of various animal tissues (especially the lysosome). It is the main member of the cysteine protease family. More than 20 species have been found in the biological world, and mainly exist in the human body11 They are closely related to human tumors, osteoporosis, arthritis and other major diseases, and they are a class of target proteases that have attracted much attention in recent years.

Figure 1. Protein structure of cathepsin.

Introductions

Protease is the main participant in human proteolysis. According to its substrate specificity, it can be divided into endopeptidase, endopeptidase, aminopeptidase and carboxypeptidase. According to its proteolytic mechanism, it can be classified as Serine proteases, cysteine proteases, aspartic proteases, threonine proteases and metalloproteases. Among them, cysteine protease has been studied more. It is widely found in viruses, bacteria, fungi, protozoa and protozoa, plants, mammals and humans, and its largest subgroup is the papain-like cysteine proteases. The papain-like cysteine protease in mammals belongs to cathepsin. It is a type of intracellular protease that mainly exists in the lysosome. It is easily activated in a weakly acidic environment. It is a type of and unstable glycoproteins in neutral solution (except cathepsin D, E, S).

Classifications

Since the concept of cathepsin was proposed in the 1920s, there have been reports from cathepsin A to cathepsin Z so far. According to the classification of proteolytic mechanism, most of the cathepsin members are cysteine proteases, and a few are aspartic proteases (cathepsin D, E) and serine proteases (cathepsin A, G); according to their substrate specificity Classification, cathepsin also includes endopeptidase-cathepsin B, F, H, K, L, S, V, peptidase-cathepsin B, C, H, X, aminopeptidase ——Cathepsin C, H, Carboxypeptidase——Cathepsin B, X.

Cathepsin B

Cathepsin B (CTSB) is a cysteine proteolytic enzyme in the lysosomal body. Its catalytic effect is realized by Cys and His. It is easily inhibited by sulfhydryl reagents. It is also called sulfhydrylase. It belongs to the papain family and has a pH of 3.0 to 7.0. Active, irreversibly inactivated under alkaline conditions.

Functions

CTSB exists in bacteria, viruses, protozoa, plants and mammals, and is distributed in liver, spleen, kidney, bone, nerve cells, interstitial fibroblasts, macrophages, etc. CB plays an essential role in the lysosomal protein degradation pathway. When extracellular proteins, plasma proteins, hormones, and phagocytosed bacteria enter the cell, they are hydrolyzed by lysosome proteolytic enzymes for intracellular digestion. Maintain a precise balance between protein synthesis and degradation.

Figure 2. Protein structure of cathepsin B.

Research

In recent years, it has been discovered that cathepsin B (CB) is related to tumor invasion and metastasis. CB can directly dissolve or indirectly activate and dissolve extracellular matrix, such as collagen, laminin, basement membrane, etc. The component enzymes promote the infiltration of tumor cells into deep tissues, thereby opening a channel for the movement of cancer cells. Studies have found that CB is highly expressed in a variety of tumor cells, such as gastric cancer, lung cancer, bowel cancer, breast cancer, prostate cancer, kidney cancer and other cancer cells; and mRNA expression is related to the histological type and differentiation stage of the cancer There is a certain relationship, but the protein level is the opposite. This difference may have some regulation at the transcription and post-transcription level, which affects the final expression; the expression of CB in pericarcinoma stromal cells and vascular endothelial cells is enhanced. Normal conditions Inferior mesenchymal fibroblasts and macrophages can also secrete CB, but the expression is significantly increased at the stage of cancer, indicating that during the process of cancer infiltration and metastasis, the excessive synthesis and leakage of macrophages CB may also participate in the spread of cancer cells Mechanism.