WIF1 explained

Wnt inhibitory factor 1 is a protein that in humans is encoded by the WIF1 gene.^[1] WIF1 is a lipid-binding protein that binds to Wnt proteins and prevents them from triggering signalling.^{[2] [3] [4]}

Function

WNT proteins are extracellular signaling molecules involved in the control of embryonic development. This gene encodes a secreted protein, which binds WNT proteins and inhibits their activities. This protein contains a WNT inhibitory factor (WIF) domain and 5 epidermal growth factor (EGF)-like domains. It may be involved in mesoderm segmentation. This protein is found to be present in fish, amphibia and mammals.

Further reading

• Shepelev MV, Korobko EV, Korobko IV . [WIF1: perspectives of application in oncology] . Mol. Gen. Mikrobiol. Virusol. . 4 . 3–7 . 2006 . 17094650 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Clark HF, Gurney AL, Abaya E, etal . The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. . Genome Res. . 13 . 10 . 2265–70 . 2003 . 12975309 . 10.1101/gr.1293003 . 403697 .
• Reguart N, He B, Xu Z, etal . Cloning and characterization of the promoter of human Wnt inhibitory factor-1. . Biochem. Biophys. Res. Commun. . 323 . 1 . 229–34 . 2004 . 15351726 . 10.1016/j.bbrc.2004.08.075 .
• Esufali S, Bapat B . Cross-talk between Rac1 GTPase and dysregulated Wnt signaling pathway leads to cellular redistribution of beta-catenin and TCF/LEF-mediated transcriptional activation. . Oncogene . 23 . 50 . 8260–71 . 2004 . 15377999 . 10.1038/sj.onc.1208007 . 30877665 .
• Ohigashi T, Mizuno R, Nakashima J, etal . Inhibition of Wnt signaling downregulates Akt activity and induces chemosensitivity in PTEN-mutated prostate cancer cells. . Prostate . 62 . 1 . 61–8 . 2005 . 15389810 . 10.1002/pros.20117 . 1398615 .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Simon M, Grandage VL, Linch DC, Khwaja A . Constitutive activation of the Wnt/beta-catenin signalling pathway in acute myeloid leukaemia. . Oncogene . 24 . 14 . 2410–20 . 2005 . 15735743 . 10.1038/sj.onc.1208431 . free .
• Taniguchi H, Yamamoto H, Hirata T, etal . Frequent epigenetic inactivation of Wnt inhibitory factor-1 in human gastrointestinal cancers. . Oncogene . 24 . 53 . 7946–52 . 2005 . 16007117 . 10.1038/sj.onc.1208910 . free .
• Lin YC, You L, Xu Z, etal . Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines. . Biochem. Biophys. Res. Commun. . 341 . 2 . 635–40 . 2006 . 16427602 . 10.1016/j.bbrc.2005.12.220 .
• Urakami S, Shiina H, Enokida H, etal . Epigenetic inactivation of Wnt inhibitory factor-1 plays an important role in bladder cancer through aberrant canonical Wnt/beta-catenin signaling pathway. . Clin. Cancer Res. . 12 . 2 . 383–91 . 2006 . 16428476 . 10.1158/1078-0432.CCR-05-1344 . 22202251 .
• Liepinsh E, Bányai L, Patthy L, Otting G . NMR structure of the WIF domain of the human Wnt-inhibitory factor-1. . J. Mol. Biol. . 357 . 3 . 942–50 . 2006 . 16476441 . 10.1016/j.jmb.2006.01.047 .
• Batra S, Shi Y, Kuchenbecker KM, etal . Wnt inhibitory factor-1, a Wnt antagonist, is silenced by promoter hypermethylation in malignant pleural mesothelioma. . Biochem. Biophys. Res. Commun. . 342 . 4 . 1228–32 . 2006 . 16516163 . 10.1016/j.bbrc.2006.02.084 .
• Chim CS, Chan WW, Pang A, Kwong YL . Preferential methylation of Wnt inhibitory factor-1 in acute promyelocytic leukemia: an independent poor prognostic factor. . Leukemia . 20 . 5 . 907–9 . 2006 . 16525492 . 10.1038/sj.leu.2404176 . free .
• Urakami S, Shiina H, Enokida H, etal . Combination analysis of hypermethylated Wnt-antagonist family genes as a novel epigenetic biomarker panel for bladder cancer detection. . Clin. Cancer Res. . 12 . 7 Pt 1 . 2109–16 . 2006 . 16609023 . 10.1158/1078-0432.CCR-05-2468 . free .
• Milutinovic S, D'Alessio AC, Detich N, Szyf M . Valproate induces widespread epigenetic reprogramming which involves demethylation of specific genes. . Carcinogenesis . 28 . 3 . 560–71 . 2007 . 17012225 . 10.1093/carcin/bgl167 . free .
• Queimado L, Lopes CS, Reis AM . WIF1, an inhibitor of the Wnt pathway, is rearranged in salivary gland tumors. . Genes Chromosomes Cancer . 46 . 3 . 215–25 . 2007 . 17171686 . 10.1002/gcc.20402 . 34184943 .
• Chan SL, Cui Y, van Hasselt A, etal . The tumor suppressor Wnt inhibitory factor 1 is frequently methylated in nasopharyngeal and esophageal carcinomas. . Lab. Invest. . 87 . 7 . 644–50 . 2007 . 17384664 . 10.1038/labinvest.3700547 . free .
• Veeck J, Wild PJ, Fuchs T, etal . Prognostic relevance of Wnt-inhibitory factor-1 (WIF1) and Dickkopf-3 (DKK3) promoter methylation in human breast cancer. . BMC Cancer . 9 . 1–13 . 2009 . 19570204 . 10.1186/1471-2407-9-217 . 2717119 . free .

Notes and References

1. Web site: Entrez Gene: WIF1 WNT inhibitory factor 1 .
2. Malinauskas T, Aricescu AR, Lu W, Siebold C, Jones EY . Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1 . Nature Structural & Molecular Biology . 18 . 8 . 886–893 . July 2011 . 21743455 . 3430870 . 10.1038/nsmb.2081 .
3. Malinauskas T . Docking of fatty acids into the WIF domain of the human Wnt inhibitory factor-1 . Lipids . 43 . 3 . 227–30 . 2008 . 18256869 . 10.1007/s11745-007-3144-3 . 31357937 .
4. Hsieh JC, Kodjabachian L, Rebbert ML, Rattner A, Smallwood PM, Samos CH, Nusse R, Dawid IB, Nathans J . A new secreted protein that binds to Wnt proteins and inhibits their activities . Nature . 398 . 6726 . 431–6 . Apr 1999 . 10201374 . 10.1038/18899 . 1999Natur.398..431H . 4376660 .