Axin-2 also known as axin-like protein (Axil) or axis inhibition protein 2 (AXIN2) or conductin is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''AXIN2''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
Function
The Axin-related protein, Axin2, presumably plays an important role in the regulation of the stability of
beta-catenin
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcripti ...
in the
Wnt signaling pathway
The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling p ...
, like its rodent homologs, mouse conductin/rat axil. In mouse, conductin organizes a multiprotein complex of
APC (adenomatous polyposis of the colon), beta-catenin,
glycogen synthase kinase 3-beta, and conductin, which leads to the degradation of beta-catenin.
The AXIN proteins attract substantial interest in cancer research as AXIN1 and AXIN2 work synergistically to control pro-oncogenic
β-catenin
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcriptio ...
signaling. Importantly, activity in the β-catenin destruction complex can be increased by tankyrase inhibitors and are a potential therapeutic option to reduce the growth of β-catenin-dependent cancers.
Clinical significance
The deregulation of beta-catenin is an important event in the genesis of a number of malignancies. The AXIN2 gene has been mapped to 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer,
neuroblastoma
Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in the ...
, and other tumors. Mutations in this gene have been associated with
colorectal cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...
with defective mismatch repair.
The most critical events of teeth, lip and palate formation occur almost concurrently.
Hypodontia
Hypodontia is defined as the developmental absence of one or more teeth excluding the third molars. It is one of the most common dental anomalies, and can have a negative impact on function, and also appearance. It rarely occurs in primary teet ...
, defined as the congenital lack of one or more permanent teeth, is the most common dental abnormality found in humans and affects approximately 20% of the population worldwide.
AXIS inhibition protein 2 (AXIN2) gene polymorphic variants may be associated with both hypodontia and oligodontia (characterized by the lack of six or more permanent teeth).
Mutations of this gene have been found in individuals with colorectal carcinomas and liver tumors.
An AXIN2 mutation (1966C>T) detected in a Finnish family was associated with both tooth agenesis and colon neoplasia. A second family is described from Michigan in 2011, with members describing severe oligodontia, sparse hair, and hundreds of colons polyps. Another family was found by the Mayo Clinic in 2019. In essence, the mutation seems to disrupt
tooth development
Tooth development or odontogenesis is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. For human teeth to have a healthy oral environment, all parts of the tooth must develop during appropriate stag ...
early in life and later contributes to the emergence of polyps and eventually colon cancer, an observation that suggests that the lack of permanent teeth may be an indicator of colon cancer susceptibility.
Dentists may at the very least need to remain aware of the possible association, to be able to detect such cases of tooth agenesis and forward the patient to more complete genetic diagnostic examinations. This is a simple example of how molecular genetic discoveries today interact with traditional disciplines (Longtin, 2004).
Interactions
AXIN2 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
GSK3B
Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the ''GSK3B'' gene. In mice, the enzyme is encoded by the Gsk3b gene. Abnormal regulation and expression of GSK-3 beta is associated with an increased suscept ...
.
Further reading
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External links
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