Cited by 181Ubiquitin and proteasome pathwaysIron Metabolism and DisordersHemoglobin structure and function

Identification of the ubiquitin–protein ligase that recognizes oxidized IRP2

Yamanaka, Koji, Ishikawa, Haruto, Megumi, Yuzuru, Tokunaga, Fuminori, Kanie, Masato, Rouault, Tracey A., Morishima, Isao, Minato, Nagahiro +2 more·2003·Nature Cell Biology

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.

Integrity signals

Registry

Crossref · 10.1038/ncb952

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Yamanaka, K., Ishikawa, H., Megumi, Y., Tokunaga, F., Kanie, M., Rouault, T. A., Morishima, I., Minato, N., Ishimori, K., & Iwai, K.
Affiliations
  • Kyoto University (JP)
  • Osaka City University (JP)
  • National Institutes of Health (US)
Venue
Nature Cell Biology
Published
2003-03-10
Volume
5
Issue
4
Pages
336-340
ISSN
  • 1465-7392 (ISSN-L)
  • 1476-4679
OpenAlex
W1998851985
Cited by
181
References
25
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 8 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 9 · 2013: 4 · 2012: 25
FWCI
5.25
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Cell Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords
IRP2, E3 ubiquitin ligase, RING finger protein, HOIL-1, ubiquitination, heme, iron sensing, protein degradation, iron metabolism
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, Eukaryotic Cells, Genetic Vectors, Heme, Humans, Iron, Ligases, Molecular Sequence Data, Mutation, Oxidation-Reduction, Transcription Factors, Gene Expression Regulation, Enzymologic, COS Cells, Ubiquitin, Iron Regulatory Protein 2, Ubiquitin-Protein Ligases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review