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Tytuł pozycji:

CDC20 promotes bone formation via APC/C dependent ubiquitination and degradation of p65.

Tytuł:
CDC20 promotes bone formation via APC/C dependent ubiquitination and degradation of p65.
Autorzy:
Du Y; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Zhang M; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Liu X; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Li Z; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Hu M; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Tian Y; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Lv L; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Zhang X; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Liu Y; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Zhang P; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Zhou Y; Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, National Clinical Research Center for Oral Diseases, Beijing Key Laboratory of Digital Stomatology, Beijing, China.
Źródło:
EMBO reports [EMBO Rep] 2021 Sep 06; Vol. 22 (9), pp. e52576. Date of Electronic Publication: 2021 Aug 12.
Typ publikacji:
Journal Article; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Publication: 2014- : London, UK : Wiley Blackwell
Original Publication: Oxford, UK : Published for EMBO by Oxford University Press, 2000-
MeSH Terms:
Cell Cycle Proteins*/genetics
Cell Cycle Proteins*/metabolism
Osteogenesis*/genetics
Anaphase-Promoting Complex-Cyclosome/genetics ; Anaphase-Promoting Complex-Cyclosome/metabolism ; Animals ; Cdc20 Proteins/genetics ; Cdc20 Proteins/metabolism ; Mice ; Ubiquitination
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Contributed Indexing:
Keywords: APC/C; BMSCs; CDC20; osteogenic differentiation; p65
Substance Nomenclature:
0 (Cdc20 Proteins)
0 (Cdc20 protein, mouse)
0 (Cell Cycle Proteins)
EC 2.3.2.27 (Anaphase-Promoting Complex-Cyclosome)
Entry Date(s):
Date Created: 20210812 Date Completed: 20211022 Latest Revision: 20220531
Update Code:
20240105
PubMed Central ID:
PMC8419691
DOI:
10.15252/embr.202152576
PMID:
34382737
Czasopismo naukowe
The E3 ubiquitin ligase complex CDC20-activated anaphase-promoting complex/Cyclosome (APC/C CDC20 ) 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 APC11 CDC20 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.
(© 2021 The Authors. Published under the terms of the CC BY 4.0 license.)

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