The serine protease TMPRSS6 is required to sense iron deficiency

被引：455

作者：

Du, Xin ^{[1
]}

She, Ellen ^{[1
]}

Gelbart, Terri ^{[2
]}

Truksa, Jaroslav ^{[2
]}

Lee, Pauline ^{[2
]}

Xia, Yu ^{[1
]}

Khovananth, Kevin ^{[1
]}

Mudd, Suzanne ^{[1
]}

Mann, Navjiwan ^{[1
]}

Moresco, Eva Marie Y. ^{[1
]}

Beutler, Ernest ^{[2
]}

Beutler, Bruce ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Genet, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

来源：

SCIENCE | 2008年 / 320卷 / 5879期

关键词：

D O I：

10.1126/science.1157121

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：1088 / 1092

页数：5

共 26 条

[21] The distal location of the iron responsive region of the hepcidin promoter [J].