GDF5 explained

Growth/differentiation factor 5 is a protein that in humans is encoded by the GDF5 gene.^{[1] [2] [3]}

The protein encoded by this gene is closely related to the bone morphogenetic protein (BMP) family and is a member of the TGF-beta superfamily. This group of proteins is characterized by a polybasic proteolytic processing site which is cleaved to produce a mature protein containing seven conserved cysteine residues. The members of this family are regulators of cell growth and differentiation in both embryonic and adult tissues. Mutations in this gene are associated with acromesomelic dysplasia, Hunter-Thompson type; brachydactyly, type C; and osteochondrodysplasia, Grebe type. These associations confirm that the gene product plays a role in skeletal development.

GDF5 is expressed in the developing central nervous system,^[4] and has a role in skeletal and joint development.^{[5] [6] [7]} It also increases the survival of neurones that respond to the neurotransmitter dopamine, and is a potential therapeutic molecule associated with Parkinson's disease.^[8]

See also

• Chondrodysplasia, Grebe type

Further reading

• Reddi AH . Cartilage morphogenesis: role of bone and cartilage morphogenetic proteins, homeobox genes and extracellular matrix . Matrix Biol. . 14 . 8 . 599–606 . 1997 . 9057810 . 10.1016/S0945-053X(05)80024-1 .
• Luyten FP . Cartilage-derived morphogenetic protein-1 . Int. J. Biochem. Cell Biol. . 29 . 11 . 1241–4 . 1998 . 9451821 . 10.1016/S1357-2725(97)00025-3 .
• Ducy P, Karsenty G . The family of bone morphogenetic proteins . Kidney Int. . 57 . 6 . 2207–14 . 2000 . 10844590 . 10.1046/j.1523-1755.2000.00081.x . free .
• Faiyaz-Ul-Haque M, Ahmad W, Wahab A . Frameshift mutation in the cartilage-derived morphogenetic protein 1 (CDMP1) gene and severe acromesomelic chondrodysplasia resembling Grebe-type chondrodysplasia . American Journal of Medical Genetics . 111 . 1 . 31–7 . 2003 . 12124730 . 10.1002/ajmg.10501 . etal. free .
• Chang SC, Hoang B, Thomas JT . Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development . J. Biol. Chem. . 269 . 45 . 28227–34 . 1994 . 10.1016/S0021-9258(18)46918-9 . 7961761 . etal. free .
• Hötten G, Neidhardt H, Jacobowsky B, Pohl J . Cloning and expression of recombinant human growth/differentiation factor 5 . Biochem. Biophys. Res. Commun. . 204 . 2 . 646–52 . 1994 . 7980526 . 10.1006/bbrc.1994.2508 .
• Thomas JT, Lin K, Nandedkar M . A human chondrodysplasia due to a mutation in a TGF-beta superfamily member . Nat. Genet. . 12 . 3 . 315–7 . 1996 . 8589725 . 10.1038/ng0396-315 . 43140478 . etal.
• Lin K, Thomas JT, McBride OW, Luyten FP . Assignment of a new TGF-beta superfamily member, human cartilage-derived morphogenetic protein-1, to chromosome 20q11.2 . Genomics . 34 . 1 . 150–1 . 1996 . 8661040 . 10.1006/geno.1996.0257 .
• Nishitoh H, Ichijo H, Kimura M . Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5 . J. Biol. Chem. . 271 . 35 . 21345–52 . 1996 . 8702914 . 10.1074/jbc.271.35.21345 . etal. free .
• Erlacher L, McCartney J, Piek E . Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis . J. Bone Miner. Res. . 13 . 3 . 383–92 . 1998 . 9525338 . 10.1359/jbmr.1998.13.3.383 . 25307046 . etal. free .
• Sugiura T, Hötten G, Kawai S . Minimal promoter components of the human growth/differentiation factor-5 gene . Biochem. Biophys. Res. Commun. . 263 . 3 . 707–13 . 1999 . 10512744 . 10.1006/bbrc.1999.1445 .
• Aoki H, Fujii M, Imamura T . Synergistic effects of different bone morphogenetic protein type I receptors on alkaline phosphatase induction . J. Cell Sci. . 114 . Pt 8 . 1483–9 . 2001 . 10.1242/jcs.114.8.1483 . 11282024 . etal.
• Deloukas P, Matthews LH, Ashurst J . The DNA sequence and comparative analysis of human chromosome 20 . Nature . 414 . 6866 . 865–71 . 2002 . 11780052 . 10.1038/414865a . 2001Natur.414..865D . etal. free .
• Faiyaz-Ul-Haque M, Ahmad W, Zaidi SH . Mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene in a kindred affected with fibular hypoplasia and complex brachydactyly (DuPan syndrome) . Clin. Genet. . 61 . 6 . 454–8 . 2003 . 12121354 . 10.1034/j.1399-0004.2002.610610.x . 28701236 . etal.

Notes and References

1. Polinkovsky A, Robin NH, Thomas JT, Irons M, Lynn A, Goodman FR, Reardon W, Kant SG, Brunner HG, van der Burgt I, Chitayat D, McGaughran J, Donnai D, Luyten FP, Warman ML . Mutations in CDMP1 cause autosomal dominant brachydactyly type C . Nat Genet . 17 . 1 . 18–9 . Oct 1997 . 9288091 . 10.1038/ng0997-18 . 2066/24464 . 6580906 . free .
2. Thomas JT, Kilpatrick MW, Lin K, Erlacher L, Lembessis P, Costa T, Tsipouras P, Luyten FP . Disruption of human limb morphogenesis by a dominant negative mutation in CDMP1 . Nat Genet . 17 . 1 . 58–64 . Oct 1997 . 9288098 . 10.1038/ng0997-58 . 31479619 .
3. Web site: Entrez Gene: GDF5 growth differentiation factor 5 (cartilage-derived morphogenetic protein-1).
4. O'Keeffe G, Dockery P, Sullivan A . Effects of growth/differentiation factor 5 on the survival and morphology of embryonic rat midbrain dopaminergic neurones in vitro . J Neurocytol . 33 . 5 . 479–88 . 2004 . 15906156 . 10.1007/s11068-004-0511-y. 25940876 .
5. Buxton P, Edwards C, Archer C, Francis-West P . Growth/differentiation factor-5 (GDF-5) and skeletal development . J Bone Joint Surg Am . 83-A Suppl 1 . Pt 1 . S23–30 . 2001 . 11263662.
6. Francis-West P, Abdelfattah A, Chen P, Allen C, Parish J, Ladher R, Allen S, MacPherson S, Luyten F, Archer C . Mechanisms of GDF-5 action during skeletal development . Development . 126 . 6 . 1305–15 . 1999 . 10.1242/dev.126.6.1305 . 10021348.
7. Francis-West P, Parish J, Lee K, Archer C . BMP/GDF-signalling interactions during synovial joint development . Cell Tissue Res . 296 . 1 . 111–9 . 1999 . 10199971 . 10.1007/s004410051272. 21942870 .
8. Sullivan A, O'Keeffe G . The role of growth/differentiation factor 5 (GDF5) in the induction and survival of midbrain dopaminergic neurones: relevance to Parkinson's disease treatment . J Anat . 207 . 3 . 219–26 . 2005 . 16185246 . 10.1111/j.1469-7580.2005.00447.x . 1571542.