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Article: E3 ubiquitin ligase Mule targets β-catenin under conditions of hyperactive Wnt signaling

TitleE3 ubiquitin ligase Mule targets β-catenin under conditions of hyperactive Wnt signaling
Authors
KeywordsColorectal cancer
Mule
Stem cells
Wnt signaling
β-catenin
Issue Date2017
Citation
Proceedings of the National Academy of Sciences of the United States of America, 2017, v. 114, n. 7, p. E1148-E1157 How to Cite?
AbstractWnt signaling, named after the secreted proteins that bind to cell surface receptors to activate the pathway, plays critical roles both in embryonic development and the maintenance of homeostasis in many adult tissues. Two particularly important cellular programs orchestrated by Wnt signaling are proliferation and stem cell self-renewal. Constitutive activation of the Wnt pathway resulting from mutation or improper modulation of pathway components contributes to cancer development in various tissues. Colon cancers frequently bear inactivating mutations of the adenomatous polyposis coli (APC) gene, whose product is an important component of the destruction complex that regulates β-catenin levels. Stabilization and nuclear localization of β-catenin result in the expression of a panel of Wnt target genes. We previously showed that Mule/Huwe1/Arf-BP1 (Mule) controls murine intestinal stem and progenitor cell proliferation by modulating the Wnt pathway via c-Myc. Here we extend our investigation of Mule's influence on oncogenesis by showing that Mule interacts directly with β-catenin and targets it for degradation under conditions of hyperactive Wnt signaling. Our findings suggest that Mule uses various mechanisms to fine-tune the Wnt pathway and provides multiple safeguards against tumorigenesis.
Persistent Identifierhttp://hdl.handle.net/10722/292999
ISSN
2023 Impact Factor: 9.4
2023 SCImago Journal Rankings: 3.737
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDominguez-Brauer, Carmen-
dc.contributor.authorKhatun, Rahima-
dc.contributor.authorElia, Andrew J.-
dc.contributor.authorThu, Kelsie L.-
dc.contributor.authorRamachandran, Parameswaran-
dc.contributor.authorBaniasadi, Shakiba P.-
dc.contributor.authorHao, Zhenyue-
dc.contributor.authorJones, Lisa D.-
dc.contributor.authorHaight, Jillian-
dc.contributor.authorSheng, Yi-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:57:39Z-
dc.date.available2020-11-17T14:57:39Z-
dc.date.issued2017-
dc.identifier.citationProceedings of the National Academy of Sciences of the United States of America, 2017, v. 114, n. 7, p. E1148-E1157-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/292999-
dc.description.abstractWnt signaling, named after the secreted proteins that bind to cell surface receptors to activate the pathway, plays critical roles both in embryonic development and the maintenance of homeostasis in many adult tissues. Two particularly important cellular programs orchestrated by Wnt signaling are proliferation and stem cell self-renewal. Constitutive activation of the Wnt pathway resulting from mutation or improper modulation of pathway components contributes to cancer development in various tissues. Colon cancers frequently bear inactivating mutations of the adenomatous polyposis coli (APC) gene, whose product is an important component of the destruction complex that regulates β-catenin levels. Stabilization and nuclear localization of β-catenin result in the expression of a panel of Wnt target genes. We previously showed that Mule/Huwe1/Arf-BP1 (Mule) controls murine intestinal stem and progenitor cell proliferation by modulating the Wnt pathway via c-Myc. Here we extend our investigation of Mule's influence on oncogenesis by showing that Mule interacts directly with β-catenin and targets it for degradation under conditions of hyperactive Wnt signaling. Our findings suggest that Mule uses various mechanisms to fine-tune the Wnt pathway and provides multiple safeguards against tumorigenesis.-
dc.languageeng-
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America-
dc.subjectColorectal cancer-
dc.subjectMule-
dc.subjectStem cells-
dc.subjectWnt signaling-
dc.subjectβ-catenin-
dc.titleE3 ubiquitin ligase Mule targets β-catenin under conditions of hyperactive Wnt signaling-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1621355114-
dc.identifier.pmid28137882-
dc.identifier.pmcidPMC5320996-
dc.identifier.scopuseid_2-s2.0-85012964623-
dc.identifier.volume114-
dc.identifier.issue7-
dc.identifier.spageE1148-
dc.identifier.epageE1157-
dc.identifier.eissn1091-6490-
dc.identifier.isiWOS:000393989300015-
dc.identifier.issnl0027-8424-

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