Cathepsin K, abbreviated CTSK, is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''CTSK''
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 ...
.
Function
The protein encoded by this gene is a
cysteine cathepsin, a
lysosomal cysteine protease involved in bone remodeling and resorption. This protein, which is a member of the peptidase C1 protein family, is expressed predominantly in
osteoclast
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...
s.
Cathepsin K is a
protease
A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalysis, catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products ...
, which is defined by its high specificity for
kinin
A kinin is any of various structurally related peptides, such as bradykinin and kallidin. They are members of the autacoid family. Kinins are peptides that are cleaved from kininogens by the process of kallikreins. Kallikreins activate kinins ...
s, that is involved in
bone resorption
Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood.
The osteoclasts are multi-nuclea ...
. The enzyme's ability to catabolize
elastin
Elastin is a protein encoded by the ''ELN'' gene in humans and several other animals. Elastin is a key component in the extracellular matrix of gnathostomes (jawed vertebrates). It is highly Elasticity (physics), elastic and present in connective ...
,
collagen
Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...
, and
gelatin
Gelatin or gelatine () is a translucent, colorless, flavorless food ingredient, commonly derived from collagen taken from animal body parts. It is brittle when dry and rubbery when moist. It may also be referred to as hydrolyzed collagen, coll ...
allows it to break down
bone
A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...
and
cartilage
Cartilage is a resilient and smooth type of connective tissue. Semi-transparent and non-porous, it is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints ...
. This catabolic activity is also partially responsible for the loss of lung elasticity and recoil in
emphysema
Emphysema is any air-filled enlargement in the body's tissues. Most commonly emphysema refers to the permanent enlargement of air spaces (alveoli) in the lungs, and is also known as pulmonary emphysema.
Emphysema is a lower respiratory tract di ...
. Cathepsin K
inhibitors show great potential in the treatment of
osteoporosis
Osteoporosis is a systemic skeletal disorder characterized by low bone mass, micro-architectural deterioration of bone tissue leading to more porous bone, and consequent increase in Bone fracture, fracture risk.
It is the most common reason f ...
. Cathepsin K is degraded by Cathepsin S, in a process referred to as Controlled Cathepsin Cannibalism.
Cathepsin K expression is stimulated by
inflammatory cytokine
Cytokines () are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling.
Cytokines are produced by a broad range of cells, including immune cells like macrophages, B cell, B lymphocytes, T cell, T lymphocytes ...
s that are released after
tissue injury.
Clinical significance
Cathepsin K is expressed in a significant fraction of human
breast cancer
Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...
s, where it could contribute to tumor invasiveness.
Mutations in this gene are the cause of
pycnodysostosis, an autosomal recessive disease characterized by
osteosclerosis and short stature.
Cathepsin K has also been found to be over-expressed in
glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is the most aggressive and most common type of cancer that originates in the brain, and has a very poor prognosis for survival. Initial signs and symptoms of glioblastoma are nons ...
.
That the expression of cathepsin K is characteristic for some cancers and not others has been documented.
Cathepsin K antibodies are marketed for research into expression of this enzyme by various cells.
had a cathepsin K inhibitor,
odanacatib, in
Phase III clinical trials for osteoporosis. In September, 2016, Merck announced they were discontinuing development of odanacatib after their own assessment of adverse events and an independent assessment showed increased risk of stroke.
Other cathepsin K inhibitors are in various stages of
development
Development or developing may refer to:
Arts
*Development (music), the process by which thematic material is reshaped
* Photographic development
*Filmmaking, development phase, including finance and budgeting
* Development hell, when a proje ...
.
Medivir has a cathepsin K inhibitor, MIV-711 (L-006235
), in Phase IIa clinical trial, as a
disease modifying osteoarthritis drug, as of October 2017.
References
Further reading
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Additional images
Image:Osteoclast1.jpg, Osteoclast
An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and bone remodeling, remodeling of bones of the vertebrate, vertebral skeleton. The osteoclast disassembles and digests th ...
External links
* The
MEROPS online database for peptidases and their inhibitors
C01.036*
{{Use dmy dates, date=April 2017
EC 3.4.22
Proteases
Cathepsins