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Cited by 980

The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.

Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors

Koo, Bon-Kyoung, Spit, Maureen, Jordens, Ingrid, Low, Teck Y., Stange, Daniel E., van de Wetering, Marc, van Es, Johan H., Mohammed, Shabaz, Heck, Albert J. R., Maurice, Madelon M., Clevers, Hans·2012·Nature
DOI 10.1038/nature11308
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Abstract

LGR5+ stem cells reside at crypt bottoms, intermingled with Paneth cells that provide Wnt, Notch and epidermal growth factor signals. Here we find that the related RNF43 and ZNRF3 transmembrane E3 ubiquitin ligases are uniquely expressed in LGR5+ stem cells. Simultaneous deletion of the two genes encoding these proteins in the intestinal epithelium of mice induces rapidly growing adenomas containing high numbers of Paneth and LGR5+ stem cells. In vitro, growth of organoids derived from these adenomas is arrested when Wnt secretion is inhibited, indicating a dependence of the adenoma stem cells on Wnt produced by adenoma Paneth cells. In the HEK293T human cancer cell line, expression of RNF43 blocks Wnt responses and targets surface-expressed frizzled receptors to lysosomes. In the RNF43-mutant colorectal cancer cell line HCT116, reconstitution of RNF43 expression removes its response to exogenous Wnt. We conclude that RNF43 and ZNRF3 reduce Wnt signals by selectively ubiquitinating frizzled receptors, thereby targeting these Wnt receptors for degradation.

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Crossref · 10.1038/nature11308

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6 of 6 references verified0 citation errors · 0 not checkable

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  • Ubiquitination events mediated by Drosophila Goliath family members regulate specific cellular events such as endocytosis and protein-protein interactions.

    “Ubiquitination events mediated by Drosophila Goliath family members have been shown to regulate specific cellular events such as endocytosis7,11 and protein-protein interactions12,13.”

    From RNF130 Regulates LDLR Availability and Plasma LDL Cholesterol Levels (2023) · cites this paper as [11]

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Research works printed but not linked: 25

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Metadata

Authors
Koo, B.-K., Spit, M., Jordens, I., Low, T. Y., Stange, D. E., van de Wetering, M., van Es, J. H., Mohammed, S., Heck, A. J. R., Maurice, M. M., & Clevers, H.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2012-08
Volume
488
Issue
7413
Pages
665-669
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/nature11308
Cited by
980
References
6
Language
en
Licence
www.springer.com/tdm (tdm)

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