GJB2

{{Short description|Protein-coding gene in the species Homo sapiens}}

Gap junction beta-2 protein (GJB2), also known as connexin 26 (Cx26) — is a protein that in humans is encoded by the GJB2 gene.

Function

Gap junctions were first characterized by electron microscopy as regionally specialized structures on plasma membranes of contacting adherent cells. These structures were shown to consist of cell-to-cell channels. Proteins, called connexins, purified from fractions of enriched gap junctions from different tissues differ. The connexins are designated by their molecular mass. Another system of nomenclature divides gap junction proteins into two categories, alpha and beta, according to sequence similarities at the nucleotide and amino acid levels. For example, CX43 (GJA1) is designated alpha-1 gap junction protein, whereas GJB1 (CX32), and GJB2 (CX26; this protein) are called beta-1 and beta-2 gap junction proteins, respectively. This nomenclature emphasizes that GJB1 and GJB2 are more homologous to each other than either of them is to gap junction protein, alpha GJA1.{{cite web | title = Entrez Gene: GJB2 gap junction protein, beta 2, 26kDa| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2706 }}

Gap junction beta-2 protein is a member of the connexin protein family and plays a crucial role in forming gap junctions, which are channels that allow the transport of nutrients, ions, and signaling molecules between adjacent cells.{{cite web | title = GJB2 gene | work = MedlinePlus | publisher = U.S. National Library of Medicine | url = https://medlineplus.gov/genetics/gene/gjb2/ }} GJB2 is widely expressed throughout the body, with particularly important functions in the inner ear and skin. In the cochlea, GJB2 is believed to be essential for maintaining proper potassium ion levels and for the maturation of certain cochlear cells, both of which are critical for the process of converting sound waves into electrical nerve impulses. In the skin, GJB2 contributes to the growth, maturation, and stability of the epidermis.

Clinical significance

Defects in this gene lead to the most common form of congenital deafness in developed countries, called DFNB1 (also known as connexin 26 deafness or GJB2-related deafness).{{cite journal | vauthors = Kelsell DP, Dunlop J, Stevens HP, Lench NJ, Liang JN, Parry G, Mueller RF, Leigh IM | title = Connexin 26 mutations in hereditary non-syndromic sensorineural deafness | journal = Nature | volume = 387 | issue = 6628 | pages = 80–83 | date = May 1997 | pmid = 9139825 | doi = 10.1038/387080a0 | s2cid = 4311728 | bibcode = 1997Natur.387...80K }} One fairly common mutation is the deletion of one guanine from a string of six, resulting in a frameshift and termination of the protein at amino acid number 13. Having two copies of this mutation results in deafness.{{cite journal | vauthors = Zytsar MV, Barashkov NA, Bady-Khoo MS, Shubina-Olejnik OA, Danilenko NG, Bondar AA, Morozov IV, Solovyev AV, Danilchenko VY, Maximov VN, Posukh OL | title = Updated carrier rates for c.35delG (GJB2) associated with hearing loss in Russia and common c.35delG haplotypes in Siberia | journal = BMC Medical Genetics | volume = 19 | issue = 1 | pages = 138 | date = August 2018 | pmid = 30086704 | pmc = 6081885 | doi = 10.1186/s12881-018-0650-5 | doi-access = free }}

Connexin 26 also plays a role in tumor suppression through mediation of the cell cycle.{{cite journal | vauthors = Tanaka M, Grossman HB | title = Connexin 26 induces growth suppression, apoptosis and increased efficacy of doxorubicin in prostate cancer cells | journal = Oncology Reports | volume = 11 | issue = 2 | pages = 537–541 | date = February 2004 | pmid = 14719096 | url = https://www.spandidos-publications.com/or/11/2/537 | access-date = 2018-02-18 | url-status = dead | archive-url = https://web.archive.org/web/20210801191234/https://www.spandidos-publications.com/or/11/2/537 | archive-date = 2021-08-01 }} The abnormal expression of Cx26, correlated with several types of human cancers, may serve as a prognostic factor for cancers such as colorectal cancer,{{cite journal | vauthors = Nomura S, Maeda K, Noda E, Inoue T, Fukunaga S, Nagahara H, Hirakawa K | title = Clinical significance of the expression of connexin26 in colorectal cancer | journal = Journal of Experimental & Clinical Cancer Research | volume = 29 | issue = 1 | pages = 79 | date = June 2010 | pmid = 20565955 | pmc = 2907868 | doi = 10.1186/1756-9966-29-79 | doi-access = free }} breast cancer,{{cite journal | vauthors = Teleki I, Krenacs T, Szasz MA, Kulka J, Wichmann B, Leo C, Papassotiropoulos B, Riemenschnitter C, Moch H, Varga Z | title = The potential prognostic value of connexin 26 and 46 expression in neoadjuvant-treated breast cancer | journal = BMC Cancer | volume = 13 | pages = 50 | date = February 2013 | pmid = 23374644 | pmc = 3583680 | doi = 10.1186/1471-2407-13-50 | doi-access = free }} and bladder cancer.{{cite journal | vauthors = Gee J, Tanaka M, Grossman HB | title = Connexin 26 is abnormally expressed in bladder cancer | language = English | journal = The Journal of Urology | volume = 169 | issue = 3 | pages = 1135–1137 | date = March 2003 | pmid = 12576868 | doi = 10.1097/01.ju.0000041954.91331.df }} Furthermore, Cx26 over-expression is suggested to promote cancer development by facilitating cell migration and invasion{{cite journal | vauthors = Kotini M, Mayor R | title = Connexins in migration during development and cancer | journal = Developmental Biology | volume = 401 | issue = 1 | pages = 143–151 | date = May 2015 | pmid = 25553982 | doi = 10.1016/j.ydbio.2014.12.023 | doi-access = free }} and by stimulating the self-perpetuation ability of cancer stem cells.{{cite journal | vauthors = Thiagarajan PS, Sinyuk M, Turaga SM, Mulkearns-Hubert EE, Hale JS, Rao V, Demelash A, Saygin C, China A, Alban TJ, Hitomi M, Torre-Healy LA, Alvarado AG, Jarrar A, Wiechert A, Adorno-Cruz V, Fox PL, Calhoun BC, Guan JL, Liu H, Reizes O, Lathia JD | title = Cx26 drives self-renewal in triple-negative breast cancer via interaction with NANOG and focal adhesion kinase | language = En | journal = Nature Communications | volume = 9 | issue = 1 | pages = 578 | date = February 2018 | pmid = 29422613 | pmc = 5805730 | doi = 10.1038/s41467-018-02938-1 | bibcode = 2018NatCo...9..578T }}

GJB2

Function

Clinical significance

See also

References

Further reading