Cell-cycle entry and exit: A tale of phosphorylation, transcription and degradation

Mammals must regulate the proliferation of stem, progenitor and differentiated cells to build, maintain, and repair tissues. Control of cell-cycle entry has been conceptualized by the restriction point, a time when cells escape the need for mitogens to complete the cell cycle. Our recent single-cell microscopy studies revealed sequential decisions to activate cyclin-dependent protein kinases (CDKs), induce E2F transcription and inactivate the E3 ubiquitin ligase APC/CCdh1 in lieu of a sharp restriction point. I will delineate core principles, molecular mechanisms and timing of this fundamental cell-fate commitment whose abnormal regulation is a main cause for cancer.