Ubiquitin ligase COP1 coordinates transcriptional programs that control cell type specification in the developing mouse brain
Copyright © 2018 the Author(s). Published by PNAS..
The E3 ubiquitin ligase CRL4COP1/DET1 is active in the absence of ERK signaling, modifying the transcription factors ETV1, ETV4, ETV5, and c-JUN with polyubiquitin that targets them for proteasomal degradation. Here we show that this posttranslational regulatory mechanism is active in neurons, with ETV5 and c-JUN accumulating within minutes of ERK activation. Mice with constitutive photomorphogenesis 1 (Cop1) deleted in neural stem cells showed abnormally elevated expression of ETV1, ETV4, ETV5, and c-JUN in the developing brain and spinal cord. Expression of c-JUN target genes Vimentin and Gfap was increased, whereas ETV5 and c-JUN both contributed to an expanded number of cells expressing genes associated with gliogenesis, including Olig1, Olig2, and Sox10. The mice had subtle morphological abnormalities in the cerebral cortex, hippocampus, and cerebellum by embryonic day 18 and died soon after birth. Elevated c-JUN, ETV5, and ETV1 contributed to the perinatal lethality, as several Cop1-deficient mice also lacking c-Jun and Etv5, or lacking Etv5 and heterozygous for Etv1, were viable.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:115 |
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| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 115(2018), 44 vom: 30. Okt., Seite 11244-11249 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Newton, Kim [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.12.2018 Date Revised 14.11.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1073/pnas.1805033115 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM289577470 |
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| 100 | 1 | |a Newton, Kim |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Ubiquitin ligase COP1 coordinates transcriptional programs that control cell type specification in the developing mouse brain |
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| 500 | |a Date Revised 14.11.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2018 the Author(s). Published by PNAS. | ||
| 520 | |a The E3 ubiquitin ligase CRL4COP1/DET1 is active in the absence of ERK signaling, modifying the transcription factors ETV1, ETV4, ETV5, and c-JUN with polyubiquitin that targets them for proteasomal degradation. Here we show that this posttranslational regulatory mechanism is active in neurons, with ETV5 and c-JUN accumulating within minutes of ERK activation. Mice with constitutive photomorphogenesis 1 (Cop1) deleted in neural stem cells showed abnormally elevated expression of ETV1, ETV4, ETV5, and c-JUN in the developing brain and spinal cord. Expression of c-JUN target genes Vimentin and Gfap was increased, whereas ETV5 and c-JUN both contributed to an expanded number of cells expressing genes associated with gliogenesis, including Olig1, Olig2, and Sox10. The mice had subtle morphological abnormalities in the cerebral cortex, hippocampus, and cerebellum by embryonic day 18 and died soon after birth. Elevated c-JUN, ETV5, and ETV1 contributed to the perinatal lethality, as several Cop1-deficient mice also lacking c-Jun and Etv5, or lacking Etv5 and heterozygous for Etv1, were viable | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a COP1 | |
| 650 | 4 | |a ETV1 | |
| 650 | 4 | |a ETV4 | |
| 650 | 4 | |a ETV5 | |
| 650 | 4 | |a c-JUN | |
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| 700 | 1 | |a Dugger, Debra L |e verfasserin |4 aut | |
| 700 | 1 | |a Sengupta-Ghosh, Arundhati |e verfasserin |4 aut | |
| 700 | 1 | |a Ferrando, Ronald E |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Felix |e verfasserin |4 aut | |
| 700 | 1 | |a Tao, Janet |e verfasserin |4 aut | |
| 700 | 1 | |a Lam, Wendy |e verfasserin |4 aut | |
| 700 | 1 | |a Haller, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Sara |e verfasserin |4 aut | |
| 700 | 1 | |a Sa, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Dunlap, Debra |e verfasserin |4 aut | |
| 700 | 1 | |a Eastham-Anderson, Jeffrey |e verfasserin |4 aut | |
| 700 | 1 | |a Ngu, Hai |e verfasserin |4 aut | |
| 700 | 1 | |a Hung, Jeffrey |e verfasserin |4 aut | |
| 700 | 1 | |a French, Dorothy M |e verfasserin |4 aut | |
| 700 | 1 | |a Webster, Joshua D |e verfasserin |4 aut | |
| 700 | 1 | |a Bolon, Brad |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jinfeng |e verfasserin |4 aut | |
| 700 | 1 | |a Reja, Rohit |e verfasserin |4 aut | |
| 700 | 1 | |a Kummerfeld, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Ying-Jiun |e verfasserin |4 aut | |
| 700 | 1 | |a Modrusan, Zora |e verfasserin |4 aut | |
| 700 | 1 | |a Lewcock, Joseph W |e verfasserin |4 aut | |
| 700 | 1 | |a Dixit, Vishva M |e verfasserin |4 aut | |
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