WIF1 binds WNTs

Stable Identifier
R-HSA-3769370
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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WNT Inhibitory factor 1 (WIF1) is a secreted antagonist of WNT signaling that acts by binding to WNTs in the extracellular space and inhibiting their interaction with the FZD receptor complex (Hsieh et al, 1999; Surmann-Schmitt et al, 2009; Malinauskas et al, 2011; Banyai et al, 2012). WIF1 consists of a WIF domain (WD; also present in RYK receptors) and 5 EGF domains (Patthy 2000; Hsieh et al, 1999). Functional studies show that the WD contributes most of the WNT-binding activity while the EGF repeats make contact with components of the extracellular matrix such as HSPGs and glypicans (Hsieh et al, 1999; Malinauskas et al, 2011; Sanchez-Hernandez et al, 2012). WIF1 is downregulated in some cancers, and overexpression of human WIF1 has been shown to inhibit growth of lung and bladder cancer cells (Mazieres et al, 2004; Kansara et al, 2009; Lin et al, 2006; Tang et al, 2009)

Literature References
PubMed ID Title Journal Year
19307728 Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice

Kansara, M, Tsang, M, Kodjabachian, L, Sims, NA, Trivett, MK, Ehrich, M, Dobrovic, A, Slavin, J, Choong, PF, Simmons, PJ, Dawid, IB, Thomas, DM

J. Clin. Invest. 2009
21743455 Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1

Malinauskas, T, Aricescu, AR, Lu, W, Siebold, C, Jones, EY

Nat. Struct. Mol. Biol. 2011
10201374 A new secreted protein that binds to Wnt proteins and inhibits their activities

Hsieh, JC, Kodjabachian, L, Rebbert, ML, Rattner, A, Smallwood, PM, Samos, CH, Nusse, R, Dawid, IB, Nathans, J

Nature 1999
19755491 Wif-1 is expressed at cartilage-mesenchyme interfaces and impedes Wnt3a-mediated inhibition of chondrogenesis

Surmann-Schmitt, C, Widmann, N, Dietz, U, Saeger, B, Eitzinger, N, Nakamura, Y, Rattel, M, Latham, R, Hartmann, C, von der Mark, H, Schett, G, von der Mark, K, Stock, M

J. Cell. Sci. 2009
19174556 WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1 arrest and growth inhibition of human invasive urinary bladder cancer cells

Tang, Y, Simoneau, AR, Liao, WX, Yi, G, Hope, C, Liu, F, Li, S, Xie, J, Holcombe, RF, Jurnak, FA, Mercola, D, Hoang, BH, Zi, X

Mol. Cancer Ther. 2009
22986341 Characterization of a Wnt-binding site of the WIF-domain of Wnt inhibitory factor-1

Bányai, L, Kerekes, K, Patthy, L

FEBS Lett. 2012
22951645 The WIF domain of the human and Drosophila Wif-1 secreted factors confers specificity for Wnt or Hedgehog

Sánchez-Hernández, D, Sierra, J, Ortigão-Farias, JR, Guerrero, I

Development 2012
15256437 Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer

Mazieres, J, He, B, You, L, Xu, Z, Lee, AY, Mikami, I, Reguart, N, Rosell, R, McCormick, F, Jablons, DM

Cancer Res. 2004
16427602 Wnt signaling activation and WIF-1 silencing in nasopharyngeal cancer cell lines

Lin, YC, You, L, Xu, Z, He, B, Mikami, I, Thung, E, Chou, J, Kuchenbecker, K, Kim, J, Raz, D, Yang, CT, Chen, JK, Jablons, DM

Biochem. Biophys. Res. Commun. 2006
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