The G2-to-M Transition Is Ensured by a Dual Mechanism that Protects Cyclin B from Degradation by Cdc20-Activated APC/C.
| Publication Type | Academic Article |
| Authors | Lara-Gonzalez P, Moyle M, Budrewicz J, Mendoza-Lopez J, Oegema K, Desai A |
| Journal | Dev Cell |
| Volume | 51 |
| Issue | 3 |
| Pagination | 313-325.e10 |
| Date Published | 10/03/2019 |
| ISSN | 1878-1551 |
| Keywords | Anaphase-Promoting Complex-Cyclosome, Caenorhabditis elegans, Cdc20 Proteins, Cyclin B, G2 Phase, Mitosis, Proteolysis |
| Abstract | In the eukaryotic cell cycle, a threshold level of cyclin B accumulation triggers the G2-to-M transition, and subsequent cyclin B destruction triggers mitotic exit. The anaphase-promoting complex/cyclosome (APC/C) is the E3 ubiquitin ligase that, together with its co-activator Cdc20, targets cyclin B for destruction during mitotic exit. Here, we show that two pathways act in concert to protect cyclin B from Cdc20-activated APC/C in G2, in order to enable cyclin B accumulation and the G2-to-M transition. The first pathway involves the Mad1-Mad2 spindle checkpoint complex, acting in a distinct manner from checkpoint signaling after mitotic entry but employing a common molecular mechanism-the promotion of Mad2-Cdc20 complex formation. The second pathway involves cyclin-dependent kinase phosphorylation of Cdc20, which is known to reduce Cdc20's affinity for the APC/C. Cooperation of these two mechanisms, which target distinct APC/C binding interfaces of Cdc20, enables cyclin B accumulation and the G2-to-M transition. |
| DOI | 10.1016/j.devcel.2019.09.005 |
| PubMed ID | 31588029 |
| PubMed Central ID | PMC7778526 |