Endofin, a novel BMP-SMAD regulator of the iron-regulatory hormone, hepcidin

Goh, Justin B., Wallace, Daniel F., Hong, Wanjin and Subramaniam, V. Nathan (2015) Endofin, a novel BMP-SMAD regulator of the iron-regulatory hormone, hepcidin. Scientific Reports, 5 13986.1-13986.12. doi:10.1038/srep13986


Author Goh, Justin B.
Wallace, Daniel F.
Hong, Wanjin
Subramaniam, V. Nathan
Title Endofin, a novel BMP-SMAD regulator of the iron-regulatory hormone, hepcidin
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2015-09-11
Sub-type Article (original research)
DOI 10.1038/srep13986
Open Access Status DOI
Volume 5
Start page 13986.1
End page 13986.12
Total pages 12
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2016
Language eng
Formatted abstract
BMP-SMAD signalling plays a crucial role in numerous biological processes including embryonic development and iron homeostasis. Dysregulation of the iron-regulatory hormone hepcidin is associated with many clinical iron-related disorders. We hypothesised that molecules which mediate BMP-SMAD signalling play important roles in the regulation of iron homeostasis and variants in these proteins may be potential genetic modifiers of iron-related diseases. We examined the role of endofin, a SMAD anchor, and show that knockdown of endofin in liver cells inhibits basal and BMP-induced hepcidin expression along with other BMP-regulated genes, ID1 and SMAD7. We show for the first time, the in situ interaction of endofin with SMAD proteins and significantly reduced SMAD phosphorylation with endofin knockdown, suggesting that endofin modulates hepcidin through BMP-SMAD signalling. Characterisation of naturally occurring SNPs show that mutations in the conserved FYVE domain result in mislocalisation of endofin, potentially affecting downstream signalling and modulating hepcidin expression. In conclusion, we have identified a hitherto unrecognised link, endofin, between the BMP-SMAD signalling pathway, and the regulation of hepcidin expression and iron homeostasis. This study further defines the molecular network involved in iron regulation and provides potential targets for the treatment of iron-related disorders.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
 
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