Control of Iron Homeostasis by an Iron-Regulated Ubiquitin Ligase

American Association for the Advancement of Science (AAAS) - Tập 326 Số 5953 - Trang 718-721 - 2009
Ajay A. Vashisht1, Kimberly B. Zumbrennen2, Xinhua Huang1, David N. Powers1, Armando Durazo3, Dahui Sun4, Nimesh Bhaskaran5, Anja Persson6, Mathias Uhlén6, Olle Sangfelt5, Charles Spruck4, Elizabeth A. Leibold2, James A. Wohlschlegel1
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA
2Departments of Medicine and Oncological Sciences, University of Utah, Salt Lake City, UT 84112, USA.
3Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA
4Sidney Kimmel Cancer Center, San Diego, CA 92121, USA
5Cancer Center Karolinska, Department of Oncology and Pathology, Karolinska Hospital, SE-171 76 Stockholm, Sweden.
6School of Biotechnology, Department of Proteomics, Royal Institute of Technology/AlbaNova, SE-106 91 Stockholm, Sweden.

Tóm tắt

Iron Sensor Intracellular iron is an essential cofactor for many proteins, but can also damage macromolecules, so its levels are carefully controlled. Cellular iron homeostasis is mediated by iron regulatory proteins that regulate the expression of genes involved in iron uptake and storage. However, it is not clear how cells sense iron bioavailability (see the Perspective by Rouault ). Using different approaches, Salahudeen et al. (p. 722 , published online 17 September) and Vashisht et al. (p. 718 , published online 17 September) have identified the F-box protein FBXL5 as a human iron sensor. FBXL5 is part of an E3 ubiquitin ligase complex that regulates the degradation of iron regulatory proteins and thereby cellular iron levels. It contains a hemerythrin domain that binds iron and acts as an iron-dependent regulatory switch, causing the degradation of FBXL5 under low iron conditions. This alternative pathway for the regulation of iron homeostasis has implications for both normal cellular physiology and disease.

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Tài liệu tham khảo

10.1146/annurev.nutr.28.061807.155521

10.1016/j.bbamcr.2006.05.004

10.1038/nchembio807

10.1074/jbc.270.37.21645

10.1016/S0021-9258(19)51075-4

10.1002/j.1460-2075.1995.tb00219.x

10.1016/S0021-9258(18)47367-X

10.1016/j.molcel.2005.05.027

10.1038/ncb952

10.1074/jbc.M302798200

10.1128/MCB.24.3.954-965.2004

10.1016/j.bbamcr.2007.07.010

10.1038/nrm1471

10.1038/nrm1547

10.1038/85686

10.1021/ac010617e

10.1038/sj.emboj.7600954

10.1128/MCB.01111-06

10.1126/science.1103786

10.1021/cr00027a008

10.1093/nar/gki408

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American Association for the Advancement of Science (AAAS)

Tập 326 Số 5953

718-721

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