The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Ligand-induced Ubiquitination of the Epidermal Growth Factor Receptor Involves the Interaction of the c-Cbl RING Finger and UbcH7
Open accessAbstract
c-Cbl plays a negative regulatory role in tyrosine kinase signaling by an as yet undefined mechanism. We demonstrate here, using the yeast two-hybrid system and an in vitro binding assay, that the c-Cbl RING finger domain interacts with UbcH7, a ubiquitin-conjugating enzyme (E2). UbcH7 interacted with the wild-type c-Cbl RING finger domain but not with a RING finger domain that lacks the amino acids that are deleted in 70Z-Cbl, an oncogenic mutant of c-Cbl. The in vitro interaction was enhanced by sequences on both the N- and C-terminal sides of the RING finger. In vivo and in vitro experiments revealed that c-Cbl and UbcH7 synergistically promote the ligand-induced ubiquitination of the epidermal growth factor receptor (EGFR). In contrast, 70Z-Cbl markedly reduced the ligand-induced, UbcH7-mediated ubiquitination of the EGFR. MG132, a proteasome inhibitor, significantly prolonged the ligand-induced phosphorylation of both the EGFR and c-Cbl. Thus, c-Cbl plays an essential role in the ligand-induced ubiquitination of the EGFR by a mechanism that involves an interaction of the RING finger domain with UbcH7. This mechanism participates in the down-regulation of tyrosine kinase receptors and loss of this function, as occurs in the naturally occurring 70Z-Cbl isoform, probably contributes to oncogenic transformation.
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Cited by
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RING Domain E3 Ubiquitin Ligases
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Metadata
- Authors
- Yokouchi, M., Kondo, T., Houghton, A., Bartkiewicz, M., Horne, W. C., Zhang, H., Yoshimura, A., & Baron, R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 274
- Issue
- 44
- Pages
- 31707-31712
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2042116027
- Cited by
- 323
- References
- 43
- FWCI
- 12.40
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Ligand-induced Ubiquitination of the Epidermal Growth Factor Receptor Involves the Interaction of the c-Cbl RING Finger and UbcH7. https://app.cochat.ai/papers/10.1074/jbc.274.44.31707
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- Yokouchi, M., Kondo, T., Houghton, A., Bartkiewicz, M., Horne, W. C., Zhang, H., Yoshimura, A., & Baron, R. (1999). Ligand-induced Ubiquitination of the Epidermal Growth Factor Receptor Involves the Interaction of the c-Cbl RING Finger and UbcH7. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.44.31707
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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