Control of Iron Homeostasis by an Iron-Regulated Ubiquitin Ligase
2009 (English)In: Science, ISSN 0036-8075, Vol. 326, no 5953, 718-721 p.Article in journal (Refereed) Published
Eukaryotic cells require iron for survival and have developed regulatory mechanisms for maintaining appropriate intracellular iron concentrations. The degradation of iron regulatory protein 2 (IRP2) in iron-replete cells is a key event in this pathway, but the E3 ubiquitin ligase responsible for its proteolysis has remained elusive. We found that a SKP1-CUL1-FBXL5 ubiquitin ligase protein complex associates with and promotes the iron-dependent ubiquitination and degradation of IRP2. The F-box substrate adaptor protein FBXL5 was degraded upon iron and oxygen depletion in a process that required an iron-binding hemerythrin-like domain in its N terminus. Thus, iron homeostasis is regulated by a proteolytic pathway that couples IRP2 degradation to intracellular iron levels through the stability and activity of FBXL5.
Place, publisher, year, edition, pages
2009. Vol. 326, no 5953, 718-721 p.
protein identification technology, element-binding protein, degradation, irp2, proteasome, pathway, oxygen
IdentifiersURN: urn:nbn:se:kth:diva-18903DOI: 10.1126/science.1176333ISI: 000271233200035ScopusID: 2-s2.0-70350613915OAI: oai:DiVA.org:kth-18903DiVA: diva2:336950
QC 201005252010-08-052010-08-052011-01-25Bibliographically approved