The G2-to-M Transition Is Ensured by a Dual Mechanism that Protects Cyclin B from Degradation by Cdc20-Activated APC/C

Dev Cell. 2019 Nov 4;51(3):313-325.e10. doi: 10.1016/j.devcel.2019.09.005. Epub 2019 Oct 3.


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.

Keywords: APC/C; Cdc20; Cdk1; Mad1; Mad2; cell division; cyclin B3; germline; mitosis; spindle checkpoint.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Animals
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / metabolism
  • Cdc20 Proteins / metabolism*
  • Cell Line, Tumor
  • Cyclin B / metabolism*
  • Cyclin-Dependent Kinases / metabolism
  • Fertility
  • G2 Phase*
  • Humans
  • Mitosis*
  • Models, Biological
  • Phosphorylation
  • Protein Binding
  • Proteolysis*
  • Spindle Apparatus / metabolism


  • Caenorhabditis elegans Proteins
  • Cdc20 Proteins
  • Cyclin B
  • Anaphase-Promoting Complex-Cyclosome
  • Cyclin-Dependent Kinases