Cathepsin B belongs to a

family Family (from ) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). It forms the basis for social order. Ideally, families offer predictabili ...

of lysosomal cysteine proteases known as the cysteine cathepsins and plays an important role in intracellular proteolysis. In humans, cathepsin B is encoded by the ''CTSB''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. Cathepsin B is upregulated in certain cancers, in pre-malignant lesions, and in various other pathological conditions.

Structure

Gene

The ''CTSB'' gene is located at

chromosome 8 Chromosome 8 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 8 spans about 146 million base pairs (the building material of DNA) and represents between 4.5 and 5.0% of the total DNA i ...

p22, consisting of 13

exons An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence i ...

. The promoter of CTSB gene contains a GC-rich region including many SP1 sites, which is similar to housekeeping genes. At least five transcript variants encoding the same protein have been found for this gene.

Protein

Cathepsin B is synthesized on the

rough endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for "little n ...

as a preproenzyme of 339

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

s with a signal peptide of 17 amino acids. Procathepsin B of 43/46 kDa is then transported to the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic Cell (biology), cells. Part of the endomembrane system in the cytoplasm, it protein targeting, packages proteins ...

, 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.

Function

Cathepsin B may enhance the activity of other proteases, including

matrix metalloproteinase Matrix metalloproteinases (MMPs), also known as matrix metallopeptidases or matrixins, are metalloproteinases that are calcium-dependent zinc-containing endopeptidases; other family members are adamalysins, serralysins, and astacins. The MMPs be ...

urokinase Urokinase, also known as urokinase-type plasminogen activator (uPA), is a serine protease present in humans and other animals. The human urokinase protein was discovered, but not named, by McFarlane and Pilling in 1947. Urokinase was originally ...

(

serine protease Serine proteases (or serine endopeptidases) are enzymes that cleave peptide bonds in proteins. Serine serves as the nucleophilic amino acid at the (enzyme's) active site. They are found ubiquitously in both eukaryotes and prokaryotes. Serin ...

urokinase plasminogen activator), and cathepsin D, and thus it has an essential position for the proteolysis of extracellular matrix components, intercellular communication disruption, and reduced protease inhibitor expression. Cells may become carcinogenic when cathepsin B is unregulated.

Potential in disease

Cathepsin B has been proposed as a potentially effective biomarker for a variety of

cancers Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...

. Overexpression of cathepsin B is correlated with invasive and metastatic cancers. Cathepsin B has been shown to be involved in the

pathogenesis In pathology, pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes . Descript ...

pancreatitis Pancreatitis is a condition characterized by inflammation of the pancreas. The pancreas is a large organ behind the stomach that produces digestive enzymes and a number of hormone A hormone (from the Ancient Greek, Greek participle , "se ...

, by prematurely activating the digestive enzyme

trypsinogen Trypsinogen () is the precursor form (or zymogen) of trypsin, a digestive enzyme. It is produced by the pancreas and found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is cleaved to its active form, trypsin, by e ...

within the pancreas, leading to autodigestion of

acinar cells Centroacinar cells are spindle-shaped cells in the exocrine pancreas. They are small and have microvilli on the apical surface. They work with organs such as the kidney, lungs, stomach, brain, intestine. The exocrine pancreas is one of two co ...

Interactions

Cathepsin B has been shown to interact with: * CTSD * CSTA, * CSTB, and *

S100A10 S100 calcium-binding protein A10 (S100A10), also known as p11, is a protein that is encoded by the ''S100A10'' gene in humans and the ''S100a10'' gene in other species. S100A10 is a member of the S100 family of proteins containing two EF-hand c ...

. Cathepsin B is inhibited by: *

Nitroxoline Nitroxoline is an antibiotic that has been in use in Europe for about fifty years, and has proven to be very effective at combating biofilm infections. Nitroxoline was shown to cause a decrease in the biofilm density of ''P. aeruginosa'' infecti ...

* CA-074

References

External links

* The MEROPS online database for peptidases and their inhibitors
C01.060
* {{Portal bar, Biology, border=no EC 3.4.22 Proteases Extracellular matrix remodeling enzymes Cathepsins