CTSS

What is CTSS protein?

CTSS (cathepsin S) gene is a protein coding gene which situated on the long arm of chromosome 1 at locus 1q21. The preproprotein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that participates in the degradation of antigenic proteins to peptides for presentation on MHC class II molecules. The mature protein cleaves the invariant chain of MHC class II molecules in endolysosomal compartments and enables the formation of antigen-MHC class II complexes and the proper display of extracellular antigenic peptides by MHC-II. The CTSS protein is consisted of 331 amino acids and its molecular mass is approximately 37.5 kDa.

What is the function of CTSS protein?

CTSS play a key role in a variety of physiological processes, especially in protein degradation and antigen presentation. As an enzyme in the lysozyme, it is involved in degrading proteins within cells, thus helping to maintain cellular homeostasis. In addition, CTSS is involved in the MHC II molecule-mediated antigen presentation process, which is critical for immune surveillance and T cell activation.

CTSS Related Signaling Pathway

CTSS plays a key role in MHC Class II molecule-mediated antigen presentation. This protein is involved in the degradation of the ingestion protein, which in turn allows the generated peptide to bind to MHC II and be presented to CD4+ T cells for recognition, triggering a specific immune response. In addition, CTSS is involved in regulating the activity of a variety of cytokines and chemokines, affecting the inflammatory response.

CTSS Related Diseases

CTSS is associated with a variety of diseases. For example, it plays a role in tumor development, promoting tumor invasion and metastasis by influencing the degradation and remodeling of the extracellular matrix. In addition, CTSS is also associated with certain autoimmune diseases such as rheumatoid arthritis and atherosclerosis.

Fig1. CTSS–Activity and Pathological Implications. (Peter Smyth, 2022)

Bioapplications of CTSS

Small molecule inhibitors targeting CTSS are being investigated for the treatment of autoimmune diseases, chronic inflammatory diseases, and cardiovascular diseases. These inhibitors can reduce CTSS activity, reduce the destruction of diseased tissue, or slow the progression of atherosclerosis.

Case study 1: Svenja Memmert, 2018

Cathepsin S is a cysteine protease, which is expressed in human periodontal ligament (PDL) cells under inflammatory and infectious conditions. This in vitro study was established to investigate the effect of cathepsin S on PDL cell wound closure. An in vitro wound healing assay was used to monitor wound closure in wounded PDL cell monolayers for 72 h in the presence and absence of cathepsin S. In addition, the effects of cathepsin S on specific markers for apoptosis and proliferation were studied at transcriptional level. Changes in the proliferation rate due to cathepsin S stimulation were analyzed by an XTT assay, and the actions of cathepsin S on cell migration were investigated via live cell tracking. Additionally, PDL cell monolayers were treated with a toll-like receptor 2 agonist in the presence and absence of a cathepsin inhibitor to examine if periodontal bacteria can alter wound closure via cathepsins. Cathepsin S enhanced significantly the in vitro wound healing rate by inducing proliferation and by increasing the speed of cell migration, but had no effect on apoptosis. Moreover, the toll-like receptor 2 agonist enhanced significantly the wound closure and this stimulatory effect was dependent on cathepsins.

Fig1. Wound closure of PDL cell monolayers in the presence or absence of CTSS (1 ng/μl) over 72 h.

Fig2. PDL cell proliferation in the presence or absence of CTSS (1 ng/μl) at 4 h and 24 h. Mean ± SEM (n = 24), * significant (p < 0.05) difference between groups.

Case study 2: Min-Chieh Hsin, 2017

Hispolon, a phenolic compound isolated from Phellinus igniarius, induces apoptosis and anti-tumor effects in cancers. However, the molecular mechanism involved in hispolon-mediated tumor-suppressing activities observed in cervical cancer is poorly characterized. Here, the researchers demonstrated that treatment with hispolon inhibited cell metastasis in two cervical cancer cell lines. In addition, the downregulation of the lysosomal protease Cathepsin S (CTSS) was critical for hispolon-mediated suppression of tumor cell metastasis in both in vitro and in vivo models. Moreover, hispolon induced autophagy, which increased LC3 conversion and acidic vesicular organelle formation. Mechanistically, hispolon inhibited the cell motility of cervical cells through the extracellular signal-regulated kinase (ERK) pathway, and blocking of the ERK pathway reversed autophagy-mediated cell motility and CTSS inhibition. The results indicate that autophagy is essential for decreasing CTSS activity to inhibit tumor metastasis by hispolon treatment in cervical cancer; this finding provides a new perspective on molecular regulation.

Fig3. HeLa cells transfected with pCMV3-CTSS-His plasmid 5 μg for 6 h and treated with hispolon for 24 h, then analyzed by Western blot and migration assay.

Fig4. The interaction between Cathepsin S, LC3 and Ubiquitin. After treating the cells with hispolon, detecting that LC3 interacted with CTSS by Co-IP.

CTSS has several biochemical functions, for example, collagen binding,cysteine-type endopeptidase activity,fibronectin binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CTSS itself. We selected most functions CTSS had, and list some proteins which have the same functions with CTSS. You can find most of the proteins on our site.

CTSS has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CTSS here. Most of them are supplied by our site. Hope this information will be useful for your research of CTSS.

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