Proto-oncogene Wnt-1 explained

Proto-oncogene Wnt-1, or Proto-oncogene Int-1 homolog is a protein that in humans is encoded by the gene.^{[1] [2]}

The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It is very conserved in evolution, and the protein encoded by this gene is known to be 98% identical to the mouse Wnt1 protein at the amino acid level. The studies in mouse indicate that the Wnt1 protein functions in the induction of the mesencephalon and cerebellum. This gene was originally considered as a candidate gene for Joubert syndrome, an autosomal recessive disorder with cerebellar hypoplasia as a leading feature. However, further studies suggested that the gene mutations might not have a significant role in Joubert syndrome. This gene is clustered with another family member, WNT10B, in the chromosome 12q13 region.^[3]

See also

• Wnt signaling pathway

Further reading

• McMahon AP, Moon RT . int-1--a proto-oncogene involved in cell signalling . Development . 107 Suppl . 161–7 . 1990 . 10.1242/dev.107.Supplement.161 . 2534596 .
• Chance PF . Clinical nosologic and genetic aspects of Joubert and related syndromes . J. Child Neurol. . 14 . 10 . 660–666 . 1999 . 10511339 . 10.1177/088307389901401007 . Cavalier L . Satran D . Pellegrino . J. E. . Koenig . M. . Dobyns . W. B. . 38298436 .
• De Ferrari GV, Moon RT . The ups and downs of Wnt signaling in prevalent neurological disorders . Oncogene . 25 . 57 . 7545–7553 . 2007 . 17143299 . 10.1038/sj.onc.1210064 . 35684619 .
• Thomas KR, Capecchi MR . Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development . Nature . 346 . 6287 . 847–850 . 1990 . 2202907 . 10.1038/346847a0 . 1990Natur.346..847T . 4341682 .
• Turc-Carel C . The human int-1 gene is located at chromosome region 12q12-12q13 and is not rearranged in myxoid liposarcoma with t(12;16) (q13;p11) . Oncogene Res. . 1 . 4 . 397–405 . 1988 . 3329717 . Pietrzak E . Kakati S . Kinniburgh . AJ . Sandberg . AA .
• Wang YK . A novel human homologue of the Drosophila frizzled wnt receptor gene binds wingless protein and is in the Williams syndrome deletion at 7q11.23 . Hum. Mol. Genet. . 6 . 3 . 465–472 . 1997 . 9147651 . 10.1093/hmg/6.3.465 . Samos CH . Peoples R . Pérez-Jurado . LA . Nusse . R . Francke . U . free .
• Bafico A . Interaction of frizzled related protein (FRP) with Wnt ligands and the frizzled receptor suggests alternative mechanisms for FRP inhibition of Wnt signaling . J. Biol. Chem. . 274 . 23 . 16180–16187 . 1999 . 10347172 . 10.1074/jbc.274.23.16180 . Gazit A . Pramila T . Finch . PW . Yaniv . A . Aaronson . SA . free .
• Gazit A . Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response . Oncogene . 18 . 44 . 5959–5966 . 1999 . 10557084 . 10.1038/sj.onc.1202985 . Yaniv A . Bafico A . Pramila . Tata . Igarashi . Makoto . Kitajewski . Jan . Aaronson . Stuart A . 2009505 .
• Lee CS . SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm . Development . 127 . 1 . 109–18 . 2000 . 10654605 . Buttitta LA . May NR . Kispert . A . Fan . CM . 10.1242/dev.127.1.109 .
• Tanaka K . The evolutionarily conserved porcupine gene family is involved in the processing of the Wnt family . Eur. J. Biochem. . 267 . 13 . 4300–4311 . 2000 . 10866835 . 10.1046/j.1432-1033.2000.01478.x . Okabayashi K . Asashima M . Perrimon . Norbert . Kadowaki . Tatsuhiko .
• Tamai K . LDL-receptor-related proteins in Wnt signal transduction . Nature . 407 . 6803 . 530–535 . 2000 . 11029007 . 10.1038/35035117 . Semenov M . Kato Y . Kato . Yoichi . Spokony . Rebecca . Liu . Chunming . Katsuyama . Yu . Hess . Fred . Saint-Jeannet . Jean-Pierre . 2000Natur.407..530T . 4400159 .
• Mao J . Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway . Mol. Cell . 7 . 4 . 801–809 . 2001 . 11336703 . 10.1016/S1097-2765(01)00224-6 . Wang J . Liu B . Pan . Weijun . Farr . Gist H . Flynn . Christopher . Yuan . Huidong . Takada . Shinji . Kimelman . David . free .
• Kirikoshi H, Sekihara H, Katoh M . WNT10A and WNT6, clustered in human chromosome 2q35 region with head-to-tail manner, are strongly coexpressed in SW480 cells . Biochem. Biophys. Res. Commun. . 283 . 4 . 798–805 . 2001 . 11350055 . 10.1006/bbrc.2001.4855 .
• Semënov MV . Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6 . Curr. Biol. . 11 . 12 . 951–961 . 2001 . 11448771 . 10.1016/S0960-9822(01)00290-1 . Tamai K . Brott BK . Kühl . Michael . Sokol . Sergei . He . Xi . 15702819 . free. 2001CBio...11..951S .
• Mizushima T . Wnt-1 but not epidermal growth factor induces beta-catenin/T-cell factor-dependent transcription in esophageal cancer cells . Cancer Res. . 62 . 1 . 277–82 . 2002 . 11782388 . Nakagawa H . Kamberov YG . Wilder . EL . Klein . PS . Rustgi . AK .
• Tice DA . Synergistic induction of tumor antigens by Wnt-1 signaling and retinoic acid revealed by gene expression profiling . J. Biol. Chem. . 277 . 16 . 14329–14335 . 2002 . 11832495 . 10.1074/jbc.M200334200 . Szeto W . Soloviev I . Rubinfeld . B . Fong . SE . Dugger . DL . Winer . J . Williams . PM . Wieand . D . free .

Notes and References

1. van Ooyen A, Kwee V, Nusse R . The nucleotide sequence of the human int-1 mammary oncogene; evolutionary conservation of coding and non-coding sequences . EMBO J . 4 . 11 . 2905–9 . Jan 1986 . 2998762 . 554596 . 10.1002/j.1460-2075.1985.tb04021.x.
2. Arheden K, Mandahl N, Strombeck B, Isaksson M, Mitelman F . Chromosome localization of the human oncogene INT1 to 12q13 by in situ hybridization . Cytogenet Cell Genet . 47 . 1–2 . 86–87 . May 1988 . 3281802 . 10.1159/000132513 .
3. Web site: Entrez Gene: WNT1 wingless-type MMTV integration site family, member 1.