Cathepsin B

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PDB 1csb EBI.jpg
Available structures
PDBOrtholog search: PDBe RCSB
AliasesCTSB, APPS, CPSB, cathepsin B, RECEUP
External IDsOMIM: 116810 MGI: 88561 HomoloGene: 37550 GeneCards: CTSB
RefSeq (mRNA)


RefSeq (protein)


Location (UCSC)Chr 8: 11.84 – 11.87 MbChr 14: 63.36 – 63.38 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

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 rokinase 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] It is also involved in autophagy and catabolism, which is advantageous in tumor malignancy, and it is possibly involved in specific immune resistance.[18] Additionally, it was recently determined to have minor ligase activity with the ability to attach peptide fragments via an amide bond.[19] Cathepsin B is crucial to the treatment of cancer because it plays a role in a number of human diseases and oncogenic processes.[20] Many studies have demonstrated a correlation between the invasive and metastatic characteristics of cancer and cathepsin B overexpression. According to studies, cells become carcinogenic when cathepsin B is not properly regulated.[21]

Clinical significance[edit]

Cathepsin B has been proposed as a potentially effective biomarker for a variety of cancers.[16][22][23][24][25][26] Overexpression of cathepsin B is correlated with invasive and metastatic cancers.[27] Cathepsin B is produced in muscle tissue during metabolism.[28] It is capable of crossing the blood–brain barrier[29] and is associated with neurogenesis, specifically in the mouse dentate gyrus. A wide array of diseases result in elevated levels of cathepsin B, which causes numerous pathological processes including cell death, inflammation, and production of toxic peptides. Focusing on neurological diseases, cathepsin B gene knockout studies in an epileptic rodent model have shown cathepsin B causes a significant amount of the apoptotic cell death that occurs as a result of inducing epilepsy.[30]

Cathepsin B inhibitor treatment of rats in which a seizure was induced resulted in improved neurological scores, learning ability and much reduced neuronal cell death and pro-apoptotic cell death peptides.[31] Similarly, cathepsin B gene knockout and cathepsin B inhibitor treatment studies in traumatic brain injury mouse models have shown that cathepsin B to be key to causing the resulting neuromuscular dysfunction, memory loss, neuronal cell death and increased production of pro-necrotic and pro-apoptotic cell death peptides.[32][33] In ischemic non-human primate and rodent models, cathepsin B inhibitor treatment prevented a significant loss of brain neurons, especially in the hippocampus.[34][35][36] In a Streptococcus pneumoniae meningitis rodent model, cathepsin B inhibitor treatment greatly improved the clinical course of the infection and reduced brain inflammation and inflammatory Interleukin-1β (IL1-β) and tumor necrosis factor-α (TNF-α).[37]

In a transgenic Alzheimer's disease (AD) animal model expressing human amyloid precursor protein (APP) containing the wild-type beta-secretase site sequence found in most AD patients or in guinea pigs, which are a natural model of human wild-type APP processing, genetically deleting the cathepsin B gene or chemically inhibiting cathepsin B brain activity resulted in a significant improvement in the memory deficits that develop in such mice and reduces levels of neurotoxic full-length Abeta(1-40/42) and the particularly pernicious pyroglutamate Abeta(3-40/42), which are thought to cause the disease.[38][39][40][41][42][43][44] In a non-transgenic senescence-accelerated mouse strain, which also has APP containing the wild-type beta-secretase site sequence, treatment with bilobalide, which is an extract of Gingko biloba leaves, also lowered brain Abeta by inhibiting cathepsin B.[45] Moreover, siRNA silencing or chemically inhibiting cathepsin B in primary rodent hippocampal cells or bovine chromaffin cells, which have human wild-type beta-secretase activity, reduces secretion of Abeta by the regulated secretory pathway.[46][47] Mutations in the CTSB gene have been linked to tropical pancreatitis, a form of chronic pancreatitis.[48]


Cathepsin B has been shown to interact with:

Cathepsin B is inhibited by:

See also[edit]


  1. ^ a b c ENSG00000285132 GRCh38: Ensembl release 89: ENSG00000164733, ENSG00000285132 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021939 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Sloane BF (April 1990). "Cathepsin B and cystatins: evidence for a role in cancer progression". Seminars in Cancer Biology. 1 (2): 137–52. PMID 2103490.
  6. ^ Chan SJ, San Segundo B, McCormick MB, Steiner DF (October 1986). "Nucleotide and predicted amino acid sequences of cloned human and mouse preprocathepsin B cDNAs". Proceedings of the National Academy of Sciences of the United States of America. 83 (20): 7721–5. Bibcode:1986PNAS...83.7721C. doi:10.1073/pnas.83.20.7721. PMC 386793. PMID 3463996.
  7. ^ Cao L, Taggart RT, Berquin IM, Moin K, Fong D, Sloane BF (February 1994). "Human gastric adenocarcinoma cathepsin B: isolation and sequencing of full-length cDNAs and polymorphisms of the gene". Gene. 139 (2): 163–9. doi:10.1016/0378-1119(94)90750-1. PMID 8112600.
  8. ^ Tong B, Wan B, Wei Z, Wang T, Zhao P, Dou Y, Lv Z, Xia Y, Dai Y (September 2014). "Role of cathepsin B in regulating migration and invasion of fibroblast-like synoviocytes into inflamed tissue from patients with rheumatoid arthritis". Clinical and Experimental Immunology. 177 (3): 586–97. doi:10.1111/cei.12357. PMC 4137842. PMID 24749816.
  9. ^ Lai WF, Chang CH, Tang Y, Bronson R, Tung CH (March 2004). "Early diagnosis of osteoarthritis using cathepsin B sensitive near-infrared fluorescent probes". Osteoarthritis and Cartilage. 12 (3): 239–44. doi:10.1016/j.joca.2003.11.005. PMID 14972341.
  10. ^ Ha SD, Ham B, Mogridge J, Saftig P, Lin S, Kim SO (January 2010). "Cathepsin B-mediated autophagy flux facilitates the anthrax toxin receptor 2-mediated delivery of anthrax lethal factor into the cytoplasm". The Journal of Biological Chemistry. 285 (3): 2120–9. doi:10.1074/jbc.M109.065813. PMC 2804368. PMID 19858192.
  11. ^ a b Yang WE, Ho CC, Yang SF, Lin SH, Yeh KT, Lin CW, Chen MK (2016). "Cathepsin B Expression and the Correlation with Clinical Aspects of Oral Squamous Cell Carcinoma". PLOS ONE. 11 (3): e0152165. Bibcode:2016PLoSO..1152165Y. doi:10.1371/journal.pone.0152165. PMC 4816521. PMID 27031837.
  12. ^ Qian F, Frankfater A, Chan SJ, Steiner DF (April 1991). "The structure of the mouse cathepsin B gene and its putative promoter". DNA and Cell Biology. 10 (3): 159–68. doi:10.1089/dna.1991.10.159. PMID 2012677.
  13. ^ "Entrez Gene: CTSB cathepsin B".
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