MicroRNA-223 Regulates Cyclin E Activity by Modulating Expression of F-box and WD-40 Domain Protein 7.
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| Title: | MicroRNA-223 Regulates Cyclin E Activity by Modulating Expression of F-box and WD-40 Domain Protein 7. |
|---|---|
| Authors: | Yanfei Xu1, Sengupta, Tanushri1 a-minella@northwestern.edu, Kukreja, Lokesh1, Minella, Alex C.1,2 a-minella@northwestern.edu |
| Source: | Journal of Biological Chemistry. 11/5/2010, Vol. 285 Issue 45, p34439-34446. 8p. |
| Subjects: | Ubiquitin, Ligases, Myc proteins, Rapamycin, Messenger RNA |
| Abstract: | F-box and WD-40 domain protein 7 (Fbw7) provides substrate specificity for the Skp1-Cullin1-F-box protein (SCF) ubiquitin ligase complex that targets multiple oncoproteins for degradation, including cyclin E, c-Myc, c-Jun, Notch, and mammalian target of rapamycin (mTOR). Fbw7 is a bona fide tumor suppressor, and loss-of-function mutations in FBXW7 have been identified in diverse human tumors. Although much is known about targets of the Fbw7 ubiquitin ligase pathway, relatively little is known about the regulation of Fbw7 expression. We identified a panel of candidate microRNA regulators of Fbw7 expression within a study of gene expression alterations in primary erythroblasts obtained from cyclin ET74A T393A knock-in mice, which have markedly dysregulated cyclin E expression. We found that overexpression of miR-223, in particular, significantly reduces FBXW7 mRNA levels, increases endogenous cyclin E protein and activity levels, and increases genomic instability. We next confirmed that miR-223 targets the FBXW7 3′-untranslated region. We then found that reduced miR-223 expression in primary mouse embryonic fibroblasts leads to increased Fbw7 expression and decreased cyclin E activity. Finally, we found that miR-223 expression is responsive to acute alterations in cyclin E regulation by the Fbw7 pathway. Together, our data indicate that miR-223 regulates Fbw7 expression and provide the first evidence that activity of the SCFFbw7 ubiquitin ligase can be modulated directly by the microRNA pathway. [ABSTRACT FROM AUTHOR] |
| Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 64434661 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: MicroRNA-223 Regulates Cyclin E Activity by Modulating Expression of F-box and WD-40 Domain Protein 7. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Yanfei+Xu%22">Yanfei Xu</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Sengupta%2C+Tanushri%22">Sengupta, Tanushri</searchLink><relatesTo>1</relatesTo><i> a-minella@northwestern.edu</i><br /><searchLink fieldCode="AR" term="%22Kukreja%2C+Lokesh%22">Kukreja, Lokesh</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Minella%2C+Alex+C%2E%22">Minella, Alex C.</searchLink><relatesTo>1,2</relatesTo><i> a-minella@northwestern.edu</i> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Journal+of+Biological+Chemistry%22">Journal of Biological Chemistry</searchLink>. 11/5/2010, Vol. 285 Issue 45, p34439-34446. 8p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Ubiquitin%22">Ubiquitin</searchLink><br /><searchLink fieldCode="DE" term="%22Ligases%22">Ligases</searchLink><br /><searchLink fieldCode="DE" term="%22Myc+proteins%22">Myc proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Rapamycin%22">Rapamycin</searchLink><br /><searchLink fieldCode="DE" term="%22Messenger+RNA%22">Messenger RNA</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: F-box and WD-40 domain protein 7 (Fbw7) provides substrate specificity for the Skp1-Cullin1-F-box protein (SCF) ubiquitin ligase complex that targets multiple oncoproteins for degradation, including cyclin E, c-Myc, c-Jun, Notch, and mammalian target of rapamycin (mTOR). Fbw7 is a bona fide tumor suppressor, and loss-of-function mutations in FBXW7 have been identified in diverse human tumors. Although much is known about targets of the Fbw7 ubiquitin ligase pathway, relatively little is known about the regulation of Fbw7 expression. We identified a panel of candidate microRNA regulators of Fbw7 expression within a study of gene expression alterations in primary erythroblasts obtained from cyclin ET74A T393A knock-in mice, which have markedly dysregulated cyclin E expression. We found that overexpression of miR-223, in particular, significantly reduces FBXW7 mRNA levels, increases endogenous cyclin E protein and activity levels, and increases genomic instability. We next confirmed that miR-223 targets the FBXW7 3′-untranslated region. We then found that reduced miR-223 expression in primary mouse embryonic fibroblasts leads to increased Fbw7 expression and decreased cyclin E activity. Finally, we found that miR-223 expression is responsive to acute alterations in cyclin E regulation by the Fbw7 pathway. Together, our data indicate that miR-223 regulates Fbw7 expression and provide the first evidence that activity of the SCFFbw7 ubiquitin ligase can be modulated directly by the microRNA pathway. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Journal of Biological Chemistry is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1074/jbc.M110.152306 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 8 StartPage: 34439 Subjects: – SubjectFull: Ubiquitin Type: general – SubjectFull: Ligases Type: general – SubjectFull: Myc proteins Type: general – SubjectFull: Rapamycin Type: general – SubjectFull: Messenger RNA Type: general Titles: – TitleFull: MicroRNA-223 Regulates Cyclin E Activity by Modulating Expression of F-box and WD-40 Domain Protein 7. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Yanfei Xu – PersonEntity: Name: NameFull: Sengupta, Tanushri – PersonEntity: Name: NameFull: Kukreja, Lokesh – PersonEntity: Name: NameFull: Minella, Alex C. IsPartOfRelationships: – BibEntity: Dates: – D: 05 M: 11 Text: 11/5/2010 Type: published Y: 2010 Identifiers: – Type: issn-print Value: 00219258 Numbering: – Type: volume Value: 285 – Type: issue Value: 45 Titles: – TitleFull: Journal of Biological Chemistry Type: main |
| ResultId | 1 |
