CDC20 promotes bone formation via APC/C dependent ubiquitination and degradation of p65
© 2021 The Authors. Published under the terms of the CC BY 4.0 license..
The E3 ubiquitin ligase complex CDC20-activated anaphase-promoting complex/Cyclosome (APC/CCDC20 ) plays a critical role in governing mitotic progression by targeting key cell cycle regulators for degradation. Cell division cycle protein 20 homolog (CDC20), the co-activator of APC/C, is required for full ubiquitin ligase activity. In addition to its well-known cell cycle-related functions, we demonstrate that CDC20 plays an essential role in osteogenic commitment of bone marrow mesenchymal stromal/stem cells (BMSCs). Cdc20 conditional knockout mice exhibit decreased bone formation and impaired bone regeneration after injury. Mechanistically, we discovered a functional interaction between the WD40 domain of CDC20 and the DNA-binding domain of p65. Moreover, CDC20 promotes the ubiquitination and degradation of p65 in an APC11-dependent manner. More importantly, knockdown of p65 rescues the bone loss in Cdc20 conditional knockout mice. Our current work reveals a cell cycle-independent function of CDC20, establishes APC11CDC20 as a pivotal regulator for bone formation by governing the ubiquitination and degradation of p65, and may pave the way for treatment of bone-related diseases.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
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| Enthalten in: |
EMBO reports - 22(2021), 9 vom: 06. Sept., Seite e52576 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Du, Yangge [VerfasserIn] |
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| Links: |
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| Themen: |
APC/C |
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| Anmerkungen: |
Date Completed 22.10.2021 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.15252/embr.202152576 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM329266063 |
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| 245 | 1 | 0 | |a CDC20 promotes bone formation via APC/C dependent ubiquitination and degradation of p65 |
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| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 The Authors. Published under the terms of the CC BY 4.0 license. | ||
| 520 | |a The E3 ubiquitin ligase complex CDC20-activated anaphase-promoting complex/Cyclosome (APC/CCDC20 ) plays a critical role in governing mitotic progression by targeting key cell cycle regulators for degradation. Cell division cycle protein 20 homolog (CDC20), the co-activator of APC/C, is required for full ubiquitin ligase activity. In addition to its well-known cell cycle-related functions, we demonstrate that CDC20 plays an essential role in osteogenic commitment of bone marrow mesenchymal stromal/stem cells (BMSCs). Cdc20 conditional knockout mice exhibit decreased bone formation and impaired bone regeneration after injury. Mechanistically, we discovered a functional interaction between the WD40 domain of CDC20 and the DNA-binding domain of p65. Moreover, CDC20 promotes the ubiquitination and degradation of p65 in an APC11-dependent manner. More importantly, knockdown of p65 rescues the bone loss in Cdc20 conditional knockout mice. Our current work reveals a cell cycle-independent function of CDC20, establishes APC11CDC20 as a pivotal regulator for bone formation by governing the ubiquitination and degradation of p65, and may pave the way for treatment of bone-related diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a APC/C | |
| 650 | 4 | |a BMSCs | |
| 650 | 4 | |a CDC20 | |
| 650 | 4 | |a osteogenic differentiation | |
| 650 | 4 | |a p65 | |
| 650 | 7 | |a Cdc20 Proteins |2 NLM | |
| 650 | 7 | |a Cdc20 protein, mouse |2 NLM | |
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| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xuejiao |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Zheng |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Menglong |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Yueming |e verfasserin |4 aut | |
| 700 | 1 | |a Lv, Longwei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yunsong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Ping |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yongsheng |e verfasserin |4 aut | |
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