突变型HFE如何导致遗传性血色素沉着症。
How mutant HFE causes hereditary hemochromatosis.
作者信息
Muckenthaler Martina U
机构信息
UNIVERSITY OF HEIDELBERG; MOLECULAR MEDICINE PARTNERSHIP UNIT.
出版信息
Blood. 2014 Aug 21;124(8):1212-3. doi: 10.1182/blood-2014-07-581744.
Abstract
In this issue of , Wu et al describe the molecular function of , 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.
摘要
在本期的[杂志名称]中，吴等人描述了[基因名称]的分子功能，该基因是遗传性血色素沉着症（HH）中最常发生突变的基因。HH是西方世界最常见的遗传性疾病。作者表明，HFE可防止骨形态发生蛋白（BMP）I型受体（Alk3）的泛素化和蛋白酶体降解，从而增加该受体在肝细胞表面的表达。因此，铁调节激素铁调素的转录被激活。
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本文引用的文献
1
HFE interacts with the BMP type I receptor ALK3 to regulate hepcidin expression.HFE与骨形态发生蛋白I型受体ALK3相互作用以调节铁调素的表达。
Blood. 2014 Aug 21;124(8):1335-43. doi: 10.1182/blood-2014-01-552281. Epub 2014 Jun 5.
2
The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation.血色病蛋白 HFE、TfR2 和 HJV 形成一个膜相关蛋白复合物，用于调节铁调素。
J Hepatol. 2012 Nov;57(5):1052-60. doi: 10.1016/j.jhep.2012.06.015. Epub 2012 Jun 21.
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Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice.BMP 型 I 受体缺失导致铁调素表达紊乱，引起小鼠铁过载。
Blood. 2011 Oct 13;118(15):4224-30. doi: 10.1182/blood-2011-03-339952. Epub 2011 Aug 12.
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Defective bone morphogenic protein signaling underlies hepcidin deficiency in HFE hereditary hemochromatosis.遗传性血色病中 HFE 缺陷导致成骨形态发生蛋白信号转导异常和铁调素缺乏。
Hepatology. 2010 Oct;52(4):1266-73. doi: 10.1002/hep.23814.
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Lack of the bone morphogenetic protein BMP6 induces massive iron overload.骨形态发生蛋白BMP6的缺失会导致大量铁过载。
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