Ctsb

Fig1. Schematic depiction of the role of CTSB in ferroptosis by activating STING1-dependent autophagy. (Feimei Kuang, 2020)

What is CTSB protein?

CTSB (cathepsin B) gene is a protein coding gene which situated on the short arm of chromosome 8 at locus 8p23. This gene encodes a member of the C1 family of peptidases. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the cathepsin B light and heavy chains, which can dimerize to form the double chain form of the enzyme. This enzyme is a lysosomal cysteine protease with both endopeptidase and exopeptidase activity that may play a role in protein turnover. It is also known as amyloid precursor protein secretase and is involved in the proteolytic processing of amyloid precursor protein (APP). The CTSB protein is consisted of 339 amino acids and its molecular mass is approximately 37.8 kDa.

What is the function of CTSB protein?

CTSB mainly plays a role in the lysosome, which is responsible for the degradation of proteins and other biological macromolecules ingested within the cell, and participates in the protein turnover and energy metabolism of the cell. CTSB is involved in the degradation of proteins and organelles in autophagy, which is crucial for maintaining the stability of the intracellular environment and cell energy balance. CTSBS are capable of cutting extracellular matrix (ECM) components such as collagen and elastin, thus participating in cell migration and tumor cell invasion and metastasis. CTSB plays a role in antigen processing, helping to cut protein substrates into smaller fragments for presentation to the immune system by the Major histocompatibility Complex (MHC).

CTSB Related Signaling Pathway

CTSB is involved in protein degradation during autophagy and interacts with autophagy related proteins such as LC3 to regulate the smooth progress of autophagy flow. CTSB can affect apoptosis through mitochondrial pathway or death receptor pathway, and also participate in the regulation of anti-apoptotic signaling pathways, such as PI3K/Akt and MAPK pathways. CTSB plays a role in tumor invasion, metastasis and angiogenesis, and interacts with molecules such as MMPs (matrix metalloproteinases) and VEGF (vascular endothelial growth factor) to affect tumor progression. CTSB is also involved in other signaling pathways, such as Wnt/β-catenin, Notch, and Hedgehog, which regulate cell proliferation, differentiation, and fate determination.

CTSB Related Diseases

CTSB proteins have been implicated in the occurrence and development of a variety of diseases, especially in metabolic diseases, cardiovascular diseases, cancers, and neurodegenerative diseases. In diabetes, CTSB is associated with the exacerbation of diabetic cardiomyopathy (DCM), affecting cardiac function and structure by promoting NLRP3-mediated pyroptosis. In the field of cancer, CTSB is involved in tumor growth, migration, invasion, and metastasis, and its overexpression is associated with poor prognosis in diseases such as breast cancer. In addition, the up-regulation of CTSB expression is related to tumor progression, and its knockdown can inhibit tumor cell proliferation and tumor formation. In neurodegenerative diseases such as Parkinson's disease, variations in the CTSB gene are associated with increased disease risk and may be involved in the disease process by affecting autophagy and apoptosis pathways.

Bioapplications of CTSB

As a key protease in lysosomes, CTSB is particularly important in tumor therapy, especially in the development of antibody drug conjugators (ADCs). ADCs is a novel drug that combines the targeting of antibodies with cytotoxic drug destruction, among which CTSB is one of the commonly used targets of enzyme lytic Linker. These linkers are designed to be specifically cut by CTSB in the tumor microenvironment, thereby releasing cytotoxic drugs that precisely kill tumor cells.