Cathepsin

Cathepsins (Ancient Greek kata- "down" and hepsein "boil"; abbreviated CTS) are proteases: proteins that break apart other proteins, found in many types of cells including those in all animals. There are approximately a dozen members of this family, which are distinguished by their structure, catalytic mechanism, and which proteins they cleave. Most of the members become activated at the low pH found in lysosomes. Thus, the activity of this family lies almost entirely within those organelles. There are, however, exceptions such as cathepsin K, which works extracellularly after secretion by osteoclasts in bone resorption.

Cathepsins have a vital role in mammalian cellular turnover, e.g. bone resorption. They degrade polypeptides and are distinguished by their substrate specificites.

Classification

• Cathepsin A (serine protease)
• Cathepsin B (cysteine protease)
• Cathepsin C (cysteine protease)
• Cathepsin D (aspartyl protease)
• Cathepsin E (aspartyl protease)
• Cathepsin F (cysteine proteinase)
• Cathepsin G (serine protease)
• Cathepsin H (cysteine protease)
• Cathepsin K (cysteine protease)
• Cathepsin L1 (cysteine protease)
• Cathepsin L2 (or V) (cysteine protease)
• Cathepsin O (cysteine protease)
• Cathepsin S (cysteine protease)
• Cathepsin W (cysteine proteinase)
• Cathepsin Z (or X) (cysteine protease)

Clinical significance

Cathepsins have been implicated in:

• Cancer^[1]
• Stroke^[2]
• Alzheimer's disease,
• Arthritis^[3]
• Ebola, Cathepsin L and to a lesser extent cathepsin B have been found to be necessary for the virus to enter host cells.
• COPD
• Chronic periodontitis
• Several ocular disorders: keratoconus, retinal detachment, age-related macular degeneration, and glaucoma.^[4]

Cathepsin A

Deficiencies in this protein are linked to multiple forms of galactosialidosis. The cathepsin A activity in lysates of metastatic lesions of malignant melanoma is significantly higher than in primary focus lysates. Cathepsin A increased in muscles moderately affected by muscular dystrophy and denervating diseases.

Cathepsin B

Cathepsin B seems to actually break down the proteins which cause amyloid plaque, the root of Alzheimer's symptoms, and may even be a pivotal part of the natural defense against this disease used by people who do not get it. Overexpression of the encoded protein, which is a member of the peptidase C1 family, has been associated with esophageal adenocarcinoma and other tumors. Cathepsin B has also been implicated in the progression of various human tumors including ovarian cancer. Cathepsin B is also involved in apoptosis as well as degradation of myofibrillar proteins in myocardial infarction.

Cathepsin D

Cathepsin D (an aspartyl protease) appears to cleave a variety of substrates such as fibronectin and laminin. High levels of this enzyme in tumor cells seems to be associated with greater invasiveness.

History

The earliest record of "cathepsin" found in the MEDLINE database (e.g. via PubMed) is from the Journal of Biological Chemistry in 1949.^[5]

However, references within this article indicate that cathepsins were first identified and named around the turn of the 20th century. Much of this earlier work was done in the laboratory of Max Bergmann, who spent the first several decades of the century defining these proteases. ^[6]

References

External links

• The MEROPS online database for peptidases and their inhibitors: A01.010
• MeSH Cathepsins