Imperial College London
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ProfessorGrahamWilliams

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Professor of Endocrinology
 
 
 
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Contact

 

+44 (0)20 3313 1383graham.williams

 
 
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Location

 

10N5Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Ruggiero:2022:10.1002/ctd2.113,
author = {Ruggiero, C and Durand, N and Jarjat, M and Barhanin, J and Ghirardello, EJ and Dack, MRG and Williams, GR and Bassett, JHD and Lalli, E},
doi = {10.1002/ctd2.113},
journal = {Clinical and Translational Discovery},
pages = {1--14},
title = {The secreted protein augurin is a novel modulator of canonical Wnt signalling involved in osteoblast differentiation},
url = {http://dx.doi.org/10.1002/ctd2.113},
volume = {2},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundECRG4/C2ORF40 is a tumour suppressor gene downregulated in several cancer types, which encodes the secreted protein augurin. A wide number of functions in health and disease have been assigned to augurin, but the signalling pathways it regulates are still poorly characterized. Augurin expression is strongly upregulated during in vitro differentiation of neonatal mouse osteoblasts.MethodsIn vitro differentiation assays of calvarial osteoblasts isolated from Ecrg4 -/- and wild-type mice; transient transfection assays using reporters activated by Wnt signalling and other signal transduction pathways; Real-time quantitative polymerase chain reaction for measurement of gene expression; protein expression in Chinese hamster ovary cells and Escherichia coli; in situ binding assays of proteins expressed as fusions to alkaline phosphatase with cells expressing various membrane receptors.ResultsOsteoblasts from Ecrg4 -/- mice have an accelerated differentiation compared to wild-type and upregulation of Wnt markers. Augurin is a specific repressor of Wnt-stimulated transcriptional activity, both when coexpressed together with the reporter and when added to the culture medium as a soluble protein. We confirmed the previously described binding of augurin to LOX1, a scavenger receptor, but an inhibitor of this molecule did not impair augurin repression of Wnt-stimulated transcription specifically. Genome-wide association studies showed an association of ECRG4 genomic variation with body height and osteoarthritis.ConclusionsOur study sheds new light on the wide spectrum of functions previously ascribed to augurin in brain function, stem cell biology, inflammation/immunity and cancer. Furthermore, our discovery paves the way to further characterization of the mechanisms involved in augurin repression of Wnt signalling and the development of agonists and antagonists for this protein, which have a wide array of potential applications in the clinic.
AU  - Ruggiero,C
AU  - Durand,N
AU  - Jarjat,M
AU  - Barhanin,J
AU  - Ghirardello,EJ
AU  - Dack,MRG
AU  - Williams,GR
AU  - Bassett,JHD
AU  - Lalli,E
DO  - 10.1002/ctd2.113
EP  - 14
PY  - 2022///
SN  - 2768-0622
SP  - 1
TI  - The secreted protein augurin is a novel modulator of canonical Wnt signalling involved in osteoblast differentiation
T2  - Clinical and Translational Discovery
UR  - http://dx.doi.org/10.1002/ctd2.113
UR  - https://onlinelibrary.wiley.com/doi/10.1002/ctd2.113
UR  - http://hdl.handle.net/10044/1/99804
VL  - 2
ER  -
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