Docking of Fatty Acids into the WIF Domain of the Human Wnt Inhibitory Factor-1

@article{Malinauskas2007DockingOF,
  title={Docking of Fatty Acids into the WIF Domain of the Human Wnt Inhibitory Factor-1},
  author={Tomas Malinauskas},
  journal={Lipids},
  year={2007},
  volume={43},
  pages={227-230}
}
Palmitoylated Wnt proteins comprise a conserved family of secreted signaling molecules associated with variety of human cancers. WIF domain of the human WIF (Wnt inhibitory factor)-1 is sufficient for Wnt binding and signaling inhibition. Detailed interactions between Wnt and WIF-1 are not known. Computational docking was employed to identify a possible fatty acid binding site in the WIF domain. A putative binding site was identified inside the domain. WIF domain exhibited the highest affinity… Expand
Modular mechanism of Wnt signaling inhibition by Wnt inhibitory factor 1
TLDR
A modular model for the localization of WIF-1 and for signal inhibition within morphogen gradients is suggested, consistent with conserved positively charged residues on EGF IV. Expand
Prediction of Structure of Human WNT-CRD (FZD) Complex for Computational Drug Repurposing
TLDR
The dimeric cysteine-rich domain was found to fit into the evolutionarily conserved U-shaped groove of WNT protein, thus providing a strong hydrophobic moiety for the frizzled receptor and serving as the largest binding pocket for WNT-FZD interaction. Expand
The Role of Glypicans in Wnt Inhibitory Factor-1 Activity and the Structural Basis of Wif1's Effects on Wnt and Hedgehog Signaling
TLDR
Zebrafish embryos and the heterologous system provided by D. melanogaster wing are used and it is shown that the Wif1 WIF domain can increase the Hh promoting activity of Shf's EGF domains, suggesting it is capable of interacting with Hh. Expand
Structural Insights into the Inhibition of Wnt Signaling by Cancer Antigen 5T4/Wnt-Activated Inhibitory Factor 1
TLDR
Crystal structures for the extracellular domain of 5T4/WAIF1 reveal a highly glycosylated, rigid core, comprising eight leucine-rich repeats (LRRs), which serves as a platform to present evolutionarily conserved surface residues in the N-terminal LRR1. Expand
ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes.
TLDR
Crystal structures and WNT-binding characteristics of extracellular regions from the Drosophila ROR and RYK orthologs Nrk and Derailed-2 are described, providing further insight into how WNTs may recruit RTK co-receptors into signaling complexes. Expand
ROR and RYK extracellular region structures suggest that receptor tyrosine kinases have distinct WNT-recognition modes
TLDR
Crystal structures and WNT-binding characteristics of extracellular regions from the Drosophila ROR and RYK orthologs Nrk (neurospecific receptor tyrosine kinase) and Derailed-2 (Drl-2) provide new insight into how WNTs recruit their RTK co-receptors into signaling complexes. Expand
WIF1 can effectively co-regulate pro-apoptotic activity through the combination with DKK1.
TLDR
The results indicate for the first time that the tumor suppressor WIF1 is involved in angiogenesis and supplies a possible molecular target for the treatment of distinct malignant cancers, as well as several other associated diseases. Expand
Wnt proteins.
TLDR
The process of maturation of Wnt from its initial translation to its eventual release from a cell and interactions in the extracellular environment is described. Expand
Secretion and extracellular space travel of Wnt proteins.
TLDR
Recent discoveries on factors and processes implicated in Wnt secretion, a highly complex, regulated secretory process that guides Wnt proteins through the exocytic pathway are reviewed. Expand
Wif-1 is expressed at cartilage-mesenchyme interfaces and impedes Wnt3a-mediated inhibition of chondrogenesis
TLDR
Wif-1 is identified as a novel extracellular Wnt modulator in cartilage biology and impaired growth of mesenchymal precursor cells and neutralised Wnt3a-mediated inhibition of chondrogenesis in micromass cultures of embryonic chick limb-bud cells. Expand
...
1
2
...

References

SHOWING 1-10 OF 16 REFERENCES
NMR structure of the WIF domain of the human Wnt-inhibitory factor-1.
TLDR
The results point to a possible role of WIF domains as a recognition motif of Wnt and Drosophila Hedgehog proteins that are activated by palmitoylation. Expand
Secreted antagonists of the Wnt signalling pathway
TLDR
The extracellular antagonists of the Wnt signalling pathway can be divided into two broad classes: members of the sFRP (secreted Frizzled-related protein) family, WIF (Wnt inhibitory factor)-1 and Cerberus, primarily bind to Wnt proteins; the second class comprises certainMembers of the Dickkopf (Dkk) family; these families have as-yet-undiscovered functions. Expand
Secreted Frizzled-related proteins: searching for relationships and patterns.
  • Steve Jones, C. Jomary
  • Biology, Medicine
  • BioEssays : news and reviews in molecular, cellular and developmental biology
  • 2002
TLDR
The abundant expression of SFRP genes in the early embryo, altered expression patterns in disease states, and potential significance in the evolution of the vertebrate body plan, make these intriguing molecules relevant to investigations in diverse fields of biology and biomedical sciences. Expand
Wnt proteins are lipid-modified and can act as stem cell growth factors
TLDR
This work isolated active Wnt molecules, including the product of the mouse Wnt3a gene, and found the proteins to be palmitoylated on a conserved cysteine, indicating that the lipid is important for signalling. Expand
A new secreted protein that binds to Wnt proteins and inhibits their activites
TLDR
Wnt-inhibitory factor-1 (WIF-1) is described, a secreted protein that binds to Wnt proteins and inhibits their activities, and results indicate that WNT proteins interact with structurally diverse extracellular inhibitors to fine-tune the spatial and temporal patterns of Wnt activity. Expand
Wnt inhibitory factor-1 gene transfer inhibits melanoma cell growth.
TLDR
The results suggest the potential for further application of WIF-1 gene therapy in melanoma with Wif-1 silencing by in vitro and in vivo studies and confirm the effect of W IF-1 expression in suppressing tumor growth by inhibition of Wnt signaling in vivo. Expand
The Wnt signaling pathway in development and disease.
TLDR
The data reveal that multiple extracellular, cytoplasmic, and nuclear regulators intricately modulate Wnt signaling levels, and that receptor-ligand specificity and feedback loops help to determine WNT signaling outputs. Expand
The extracellular matrix component WIF-1 is expressed during, and can modulate, retinal development
TLDR
WIF-1 and Wnt4, both components of the ECM, regulate mammalian photoreceptor development and are suggested to interact during rod production. Expand
WIF1, an inhibitor of the Wnt pathway, is rearranged in salivary gland tumors
TLDR
The identification of the WNT inhibitory factor 1 (WIF1) gene as a novel HMGA2 fusion partner in a salivary gland pleomorphic adenoma is reported, the first report suggesting that WIF1 is a recurrent target in human salivaries gland oncogenesis and that downregulation of Wif1 plays a role in the development and/or progression of pleomorphicAdenomas. Expand
Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction
TLDR
Dkk-1 is a potent antagonist of Wnt signalling, suggesting that dkk genes encode a family of secreted Wnt inhibitors. Expand
...
1
2
...