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Comment
. 2014 Aug 21;124(8):1212-3.
doi: 10.1182/blood-2014-07-581744.

How mutant HFE causes hereditary hemochromatosis

Martina U Muckenthaler  1
Affiliations
Comment

How mutant HFE causes hereditary hemochromatosis

Martina U Muckenthaler. Blood. .

Abstract

In this issue of Blood, Wu et al describe the molecular function of HFE, the gene most commonly mutated in hereditary hemochromatosis (HH). HH is the most frequent genetic disorder of the Western world. The authors show that HFE prevents ubiquitination and proteasomal degradation of bone-morphogenetic protein (BMP) receptor type I (Alk3), thereby increasing expression of this receptor on the cell surface of hepatocytes. As a consequence, transcription of the iron-hormone hepcidin is activated.

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Conflict of interest statement

Conflict-of-interest disclosure: M.U.M. received consulting fees from Novartis.

Figures

None
Regulated protein-protein interactions among HFE, TfR2, HJV (proteins mutated in HH), BMP receptors, and BMP ligands play a critical role in the “sensing” of transferrin-bound Fe to control hepcidin expression in hepatocytes. HFE binds to BMP receptor type I (Alk3) to prevent its ubiquitination and proteasomal degradation. As a result, expression of ALK3 is increased on the cell surface, activating BMP/SMAD signaling and hepcidin transcription. Professional illustration by Tom Webster, Lineworks, Inc.
See this image and copyright information in PMC

Comment on

References

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