An E3 Ligase Possessing an Iron-Responsive Hemerythrin Domain Is a Regulator of Iron Homeostasis

被引：321

作者：

Salahudeen, Ameen A. ^{[1
]}

Thompson, Joel W. ^{[1
]}

Ruiz, Julio C. ^{[1
]}

Ma, He-Wen ^{[1
]}

Kinch, Lisa N. ^{[1
]}

Li, Qiming ^{[1
]}

Grishin, Nick V. ^{[1
]}

Bruick, Richard K. ^{[1
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

来源：

SCIENCE | 2009年 / 326卷 / 5953期

关键词：

DEPENDENT DEGRADATION; MOLECULAR CONTROL; BINDING PROTEIN; IRP2; UBIQUITINATION; RNA;

D O I：

10.1126/science.1176326

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：

Cellular iron homeostasis is maintained by the coordinate posttranscriptional regulation of genes responsible for iron uptake, release, use, and storage through the actions of the iron regulatory proteins IRP1 and IRP2. However, the manner in which iron levels are sensed to affect IRP2 activity is poorly understood. We found that an E3 ubiquitin ligase complex containing the FBXL5 protein targets IRP2 for proteasomal degradation. The stability of FBXL5 itself was regulated, accumulating under iron-and oxygen-replete conditions and degraded upon iron depletion. FBXL5 contains an iron-and oxygen-binding hemerythrin domain that acted as a ligand-dependent regulatory switch mediating FBXL5's differential stability. These observations suggest a mechanistic link between iron sensing via the FBXL5 hemerythrin domain, IRP2 regulation, and cellular responses to maintain mammalian iron homeostasis.

引用

页码：722 / 726

页数：5

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