FGF3 explained

INT-2 proto-oncogene protein also known as FGF-3 is a protein that in humans is encoded by the FGF3 gene.^[1]

Function

FGF-3 is a member of the fibroblast growth factor family. FGF3 binds to Fibroblast Growth Factor Receptor 3 (FGFR3) to serve as a negative regulator of bone growth during ossification. Effectively, FGF-3 inhibits proliferation of chondrocytes within growth plate.

FGF family members possess broad mitogenic and cell survival activities and are involved in a variety of biological processes including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion.^[1]

Clinical significance

The FGF3 gene was identified by its similarity with mouse fgf3/int-2, a proto-oncogene activated in virally induced mammary tumors in the mouse. Frequent amplification of this gene has been found in human tumors, which may be important for neoplastic transformation and tumor progression. Studies of the similar genes in mouse and chicken suggested the role in inner ear formation.^[1] Also, haploinsufficiency in the FGF3 gene is thought to cause otodental syndrome.

Interactions

FGF3 (gene) has been shown to interact with EBNA1BP2.^[2]

Further reading

• Represa J, León Y, Miner C, Giraldez F . The int-2 proto-oncogene is responsible for induction of the inner ear. . Nature . 353 . 6344 . 561–3 . 1991 . 1922362 . 10.1038/353561a0 . 1991Natur.353..561R . 1375659 .
• Brookes S, Smith R, Casey G, Dickson C, Peters G . Sequence organization of the human int-2 gene and its expression in teratocarcinoma cells. . Oncogene . 4 . 4 . 429–36 . 1989 . 2470007 .
• Casey G, Smith R, McGillivray D, Peters G, Dickson C . Characterization and chromosome assignment of the human homolog of int-2, a potential proto-oncogene. . Mol. Cell. Biol. . 6 . 2 . 502–10 . 1987 . 3023852 . 367539 . 10.1128/mcb.6.2.502.
• Mansour SL, Goddard JM, Capecchi MR . Mice homozygous for a targeted disruption of the proto-oncogene int-2 have developmental defects in the tail and inner ear. . Development . 117 . 1 . 13–28 . 1993 . 10.1242/dev.117.1.13 . 8223243 . free .
• Ornitz DM, Xu J, Colvin JS, McEwen DG, MacArthur CA, Coulier F, Gao G, Goldfarb M . Receptor specificity of the fibroblast growth factor family. . J. Biol. Chem. . 271 . 25 . 15292–7 . 1996 . 8663044 . 10.1074/jbc.271.25.15292 . free .
• Galdemard C, Yamagata H, Brison O, Lavialle C . Regulation of FGF-3 gene expression in tumorigenic and non-tumorigenic clones of a human colon carcinoma cell line. . J. Biol. Chem. . 275 . 23 . 17364–73 . 2000 . 10749884 . 10.1074/jbc.M909316199 . free .
• Reimers K, Antoine M, Zapatka M, Blecken V, Dickson C, Kiefer P . NoBP, a nuclear fibroblast growth factor 3 binding protein, is cell cycle regulated and promotes cell growth. . Mol. Cell. Biol. . 21 . 15 . 4996–5007 . 2001 . 11438656 . 87226 . 10.1128/MCB.21.15.4996-5007.2001 .
• Popovici C, Conchonaud F, Birnbaum D, Roubin R . Functional phylogeny relates LET-756 to fibroblast growth factor 9. . J. Biol. Chem. . 279 . 38 . 40146–52 . 2004 . 15199049 . 10.1074/jbc.M405795200 . free .
• Antoine M, Reimers K, Wirz W, Gressner AM, Müller R, Kiefer P . Fibroblast growth factor 3, a protein with a dual subcellular fate, is interacting with human ribosomal protein S2. . Biochem. Biophys. Res. Commun. . 338 . 2 . 1248–55 . 2006 . 16263090 . 10.1016/j.bbrc.2005.10.079 .
• Tekin M, Hişmi BO, Fitoz S, Ozdağ H, Cengiz FB, Sirmaci A, Aslan I, Inceoğlu B, Yüksel-Konuk EB, Yilmaz ST, Yasun O, Akar N . Homozygous mutations in fibroblast growth factor 3 are associated with a new form of syndromic deafness characterized by inner ear agenesis, microtia, and microdontia. . Am. J. Hum. Genet. . 80 . 2 . 338–44 . 2007 . 17236138 . 1785350 . 10.1086/510920 .
• Riley BM, Mansilla MA, Ma J, Daack-Hirsch S, Maher BS, Raffensperger LM, Russo ET, Vieira AR, Dodé C, Mohammadi M, Marazita ML, Murray JC . Impaired FGF signaling contributes to cleft lip and palate. . Proc. Natl. Acad. Sci. U.S.A. . 104 . 11 . 4512–7 . 2007 . 17360555 . 1810508 . 10.1073/pnas.0607956104 . 2007PNAS..104.4512R . free .

Notes and References

1. Web site: Entrez Gene: FGF3 fibroblast growth factor 3 (murine mammary tumor virus integration site (v-int-2) oncogene homolog).
2. Reimers K, Antoine M, Zapatka M, Blecken V, Dickson C, Kiefer P . NoBP, a nuclear fibroblast growth factor 3 binding protein, is cell cycle regulated and promotes cell growth . Mol. Cell. Biol. . 21 . 15 . 4996–5007 . Aug 2001 . 11438656 . 87226 . 10.1128/MCB.21.15.4996-5007.2001 .