| First Author | Du Y | Year | 2021 |
| Journal | EMBO Rep | Volume | 22 |
| Issue | 9 | Pages | e52576 |
| PubMed ID | 34382737 | Mgi Jnum | J:314351 |
| Mgi Id | MGI:6764138 | Doi | 10.15252/embr.202152576 |
| Citation | Du Y, et al. (2021) CDC20 promotes bone formation via APC/C dependent ubiquitination and degradation of p65. EMBO Rep 22(9):e52576 |
| abstractText | 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. |
