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丝氨酸蛋白酶TMPRSS6是感知缺铁所必需的。

The serine protease TMPRSS6 is required to sense iron deficiency.

作者信息

Du Xin, She Ellen, Gelbart Terri, Truksa Jaroslav, Lee Pauline, Xia Yu, Khovananth Kevin, Mudd Suzanne, Mann Navjiwan, Moresco Eva Marie Y, Beutler Ernest, Beutler Bruce

机构信息

Department of Genetics, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Science. 2008 May 23;320(5879):1088-92. doi: 10.1126/science.1157121. Epub 2008 May 1.

Abstract

Hepcidin, a liver-derived protein that restricts enteric iron absorption, is the key regulator of body iron content. Several proteins induce expression of the hepcidin-encoding gene Hamp in response to infection or high levels of iron. However, mechanism(s) of Hamp suppression during iron depletion are poorly understood. We describe mask: a recessive, chemically induced mutant mouse phenotype, characterized by progressive loss of body (but not facial) hair and microcytic anemia. The mask phenotype results from reduced absorption of dietary iron caused by high levels of hepcidin and is due to a splicing defect in the transmembrane serine protease 6 gene Tmprss6. Overexpression of normal TMPRSS6 protein suppresses activation of the Hamp promoter, and the TMPRSS6 cytoplasmic domain mediates Hamp suppression via proximal promoter element(s). TMPRSS6 is an essential component of a pathway that detects iron deficiency and blocks Hamp transcription, permitting enhanced dietary iron absorption.

摘要

铁调素是一种由肝脏产生的限制肠道铁吸收的蛋白质,是机体铁含量的关键调节因子。几种蛋白质会在感染或铁水平升高时诱导铁调素编码基因Hamp的表达。然而,铁缺乏时Hamp抑制的机制尚不清楚。我们描述了mask:一种隐性的、化学诱导的突变小鼠表型,其特征是身体(而非面部)毛发逐渐脱落和小细胞性贫血。mask表型是由于高水平的铁调素导致膳食铁吸收减少所致,是由跨膜丝氨酸蛋白酶6基因Tmprss6的剪接缺陷引起的。正常TMPRSS6蛋白的过表达抑制Hamp启动子的激活,并且TMPRSS6胞质结构域通过近端启动子元件介导Hamp抑制。TMPRSS6是检测铁缺乏并阻断Hamp转录的途径的重要组成部分,从而允许增强膳食铁吸收。

相似文献

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The serine protease TMPRSS6 is required to sense iron deficiency.丝氨酸蛋白酶TMPRSS6是感知缺铁所必需的。
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Dietary Iron Absorption: Biochemical and Nutritional Aspects.膳食铁吸收:生化与营养方面
Adv Exp Med Biol. 2025;1480:75-87. doi: 10.1007/978-3-031-92033-2_6.

本文引用的文献

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The distal location of the iron responsive region of the hepcidin promoter.铁调素启动子铁反应区域的远端位置。
Blood. 2007 Nov 1;110(9):3436-7. doi: 10.1182/blood-2007-05-091108. Epub 2007 Jul 20.
7
Regulation of iron metabolism by hepcidin.铁调素对铁代谢的调节作用。
Annu Rev Nutr. 2006;26:323-42. doi: 10.1146/annurev.nutr.26.061505.111303.

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