Identification of the Point of No Return for Cell-Cycle Entry
How cells make the decision to divide is a fundamental process in biology, and when this decision process is perturbed cancer or developmental diseases can occur. It was previously thought that the presence or absence of external growth factors or mitogens was the primary signal telling a cell when to enter the cell cycle and divide. In the June 30th issue of Cell, Dr. Steven Cappell, working with his colleagues in the Meyer Lab, shows how diverse cellular stresses can over-ride mitogen signaling and send cells back to a quiescent state. However, once the Anaphase Promoting Complex/Cyclosome (APC/C) is irreversibly inactivated at the onset of S phase, cells become committed to the cell cycle and can no longer return to quiescence. Thus, cells execute the decision to divide just prior to replicating their DNA by inactivating the APC/C, ensuring that a damaged cell can still exit the cell cycle until the last moment. These results provide both a basic understanding of how cells replicate and have potential clinical applications for diseases such as cancer, wound healing, and neurodegenerative diseases, all of which involve the need to regulate the rate of proliferation.
Cappell SD, Chung M, Jaimovich A, Spencer SL, Meyer T. Irreversible APC(Cdh1) Inactivation Underlies the Point of No Return for Cell-Cycle Entry. Cell. 2016 Jun 30;166(1):167-80. PMID:27368103. [PubMed]