The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator
The Mediator complex is an essential transcription regulator that bridges transcription factors with RNA polymerase II. This interaction is controlled by dynamic interactions between Mediator and the CDK8 module, but the mechanisms governing CDK8 module-Mediator association remain poorly understood. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association. Our work reveals a novel mechanism regulating CDK8 module-Mediator association and suggests an expanded role for Fbw7 in transcriptional control and an unanticipated relationship with the CDK8 oncogene.
| Errataetall: |
CommentIn: Nat Rev Cancer. 2013 Mar;13(3):146. - PMID 23363990 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2013 |
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| Erschienen: |
2013 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Genes & development - 27(2013), 2 vom: 15. Jan., Seite 151-6 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Davis, Michael A [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 08.03.2013 Date Revised 21.10.2021 published: Print-Electronic CommentIn: Nat Rev Cancer. 2013 Mar;13(3):146. - PMID 23363990 Citation Status MEDLINE |
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| doi: |
10.1101/gad.207720.112 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM224200305 |
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| 100 | 1 | |a Davis, Michael A |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The SCF-Fbw7 ubiquitin ligase degrades MED13 and MED13L and regulates CDK8 module association with Mediator |
| 264 | 1 | |c 2013 | |
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| 500 | |a Date Completed 08.03.2013 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Nat Rev Cancer. 2013 Mar;13(3):146. - PMID 23363990 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The Mediator complex is an essential transcription regulator that bridges transcription factors with RNA polymerase II. This interaction is controlled by dynamic interactions between Mediator and the CDK8 module, but the mechanisms governing CDK8 module-Mediator association remain poorly understood. We show that Fbw7, a tumor suppressor and ubiquitin ligase, binds to CDK8-Mediator and targets MED13/13L for degradation. MED13/13L physically link the CDK8 module to Mediator, and Fbw7 loss increases CDK8 module-Mediator association. Our work reveals a novel mechanism regulating CDK8 module-Mediator association and suggests an expanded role for Fbw7 in transcriptional control and an unanticipated relationship with the CDK8 oncogene | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a MED13 protein, human |2 NLM | |
| 650 | 7 | |a MED13L protein, human |2 NLM | |
| 650 | 7 | |a Mediator Complex |2 NLM | |
| 650 | 7 | |a SKP Cullin F-Box Protein Ligases |2 NLM | |
| 650 | 7 | |a EC 2.3.2.27 |2 NLM | |
| 650 | 7 | |a Cyclin-Dependent Kinase 8 |2 NLM | |
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| 700 | 1 | |a Larimore, Elizabeth A |e verfasserin |4 aut | |
| 700 | 1 | |a Fissel, Brian M |e verfasserin |4 aut | |
| 700 | 1 | |a Swanger, Jherek |e verfasserin |4 aut | |
| 700 | 1 | |a Taatjes, Dylan J |e verfasserin |4 aut | |
| 700 | 1 | |a Clurman, Bruce E |e verfasserin |4 aut | |
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