Cathepsin B belongs to a family of lysosomal cysteine proteases known as the cysteine cathepsins and plays an important role in intracellular proteolysis. [5] In humans, cathepsin B is encoded by the CTSB gene. [6] [7] Cathepsin B is upregulated in certain cancers, in pre-malignant lesions, and in various other pathological conditions. [8] [9] [10] [11]
The CTSB gene is located at chromosome 8p22, consisting of 13 exons. The promoter of CTSB gene contains a GC-rich region including many SP1 sites, which is similar to housekeeping genes. [12] At least five transcript variants encoding the same protein have been found for this gene. [13]
Cathepsin B is synthesized on the rough endoplasmic reticulum as a preproenzyme of 339 amino acids with a signal peptide of 17 amino acids. [14] [15] Procathepsin B of 43/46 kDa is then transported to the Golgi apparatus, where cathepsin B is formed. Mature cathepsin B is composed of a heavy chain of 25-26 kDa and a light chain of 5kDa, which are linked by a dimer of disulfide.
Cathepsin B may enhance the activity of other proteases, including matrix metalloproteinase, urokinase (serine protease urokinase plasminogen activator), and cathepsin D, [16] [17] and thus it has an essential position for the proteolysis of extracellular matrix components, intercellular communication disruption, and reduced protease inhibitor expression. [11]
Cells may become carcinogenic when cathepsin B is unregulated. [18]
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Cathepsin B has been proposed as a potentially effective biomarker for a variety of cancers. [16] [19] Overexpression of cathepsin B is correlated with invasive and metastatic cancers. [20]
Cathepsin B has been shown to interact with:
Cathepsin B is inhibited by:
Cathepsin S is a protein that in humans is encoded by the CTSS gene. Transcript variants utilizing alternative polyadenylation signals exist for this gene.
Cathepsin O is an enzyme that in humans is encoded by the CTSO gene.
Cathepsin G is a protein that in humans is encoded by the CTSG gene. It is one of the three serine proteases of the chymotrypsin family that are stored in the azurophil granules, and also a member of the peptidase S1 protein family. Cathepsin G plays an important role in eliminating intracellular pathogens and breaking down tissues at inflammatory sites, as well as in anti-inflammatory response.
Cathepsin D is a protein that in humans is encoded by the CTSD gene. This gene encodes a lysosomal aspartyl protease composed of a protein dimer of disulfide-linked heavy and light chains, both produced from a single protein precursor. Cathepsin D is an aspartic endo-protease that is ubiquitously distributed in lysosomes. The main function of cathepsin D is to degrade proteins and activate precursors of bioactive proteins in pre-lysosomal compartments. This proteinase, which is a member of the peptidase A1 family, has a specificity similar to but narrower than that of pepsin A. Transcription of the CTSD gene is initiated from several sites, including one that is a start site for an estrogen-regulated transcript. Mutations in this gene are involved in the pathogenesis of several diseases, including breast cancer and possibly Alzheimer disease. Homozygous deletion of the CTSD gene leads to early lethality in the postnatal phase. Deficiency of CTSD gene has been reported an underlying cause of neuronal ceroid lipofuscinosis (NCL).
Cathepsin L1 is a protein that in humans is encoded by the CTSL1 gene. The protein is a cysteine cathepsin, a lysosomal cysteine protease that plays a major role in intracellular protein catabolism.
Cystatin-A is a protein that in humans is encoded by the CSTA gene.
Cystatin-B is a protein that in humans is encoded by the CSTB gene.
Cathepsin H is a protein that in humans is encoded by the CTSH gene.
Cystatin-SN is a protein that in humans is encoded by the CST1 gene.
Cystatin-SA is a protein that in humans is encoded by the CST2 gene.
Cystatin-M is a protein that in humans is encoded by the CST6 gene.
Cystatin-F is a protein that in humans is encoded by the CST7 gene.
Cystatin-D is a protein that in humans is encoded by the CST5 gene.
Cathepsin Z, also called cathepsin X or cathepsin P, is a protein that in humans is encoded by the CTSZ gene. It is a member of the cysteine cathepsin family of cysteine proteases, which has 11 members. As one of the 11 cathepsins, cathepsin Z contains distinctive features from others. Cathepsin Z has been reported involved in cancer malignancy and inflammation.
Cathepsin L2 is a protein encoded in humans by the CTSV gene.
Cathepsin W is a protein that in humans is encoded by the CTSW gene.
Serpin B13 is a protein that in humans is encoded by the SERPINB13 gene.
Cathepsin F is a protein that in humans is encoded by the CTSF gene.
Cystatin-9-like is a protein that in humans is encoded by the CST9L gene.
Cystatin-11 is a protein that in humans is encoded by the CST11 gene.
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