RRC ID 32578
Author Yamanaka K, Ishikawa H, Megumi Y, Tokunaga F, Kanie M, Rouault TA, Morishima I, Minato N, Ishimori K, Iwai K.
Title Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2.
Journal Nat. Cell Biol.
Abstract The ubiquitin system is involved in several basic cellular functions. Ubiquitination is carried out by a cascade of three reactions catalysed by the E1, E2 and E3 enzymes. Among these, the E3 ubiquitin-protein ligases have a pivotal role in determining the specificity of the system by recognizing the target substrates through defined targeting motifs. Although RING finger proteins constitute an important family of E3 ligases, only a few post-transcriptional modifications, including phosphorylation, proline hydroxylation and glycosylation, are known to function as recognition signals for E3. Iron regulatory protein 2 (IRP2), a modulator of iron metabolism, is regulated by iron-induced ubiquitination and degradation. Here we show that the RING finger protein HOIL-1 functions as an E3 ligase for oxidized IRP2, suggesting that oxidation is a specific recognition signal for ubiquitination. The oxidation of IRP2 is generated by haem, which binds to IRP2 in iron-rich cells, and by oxygen, indicating that the iron sensing of IRP2 depends on the synthesis and availability of haem.
Volume 5(4)
Pages 336-40
Published 2003-4
DOI 10.1038/ncb952
PII ncb952
PMID 12629548
MeSH Amino Acid Sequence / genetics Animals Base Sequence / genetics COS Cells Cloning, Molecular Eukaryotic Cells / enzymology* Gene Expression Regulation, Enzymologic / genetics Genetic Vectors Heme / metabolism Humans Iron / metabolism* Iron Regulatory Protein 2 / genetics Iron Regulatory Protein 2 / metabolism* Ligases / genetics Ligases / isolation & purification* Molecular Sequence Data Mutation / genetics Oxidation-Reduction Transcription Factors Ubiquitin / metabolism* Ubiquitin-Protein Ligases
IF 19.064
Times Cited 117
DNA material BS-KS HOIL-1 (RDB04183)