On page 157, Sarmento and colleagues show how the developmental regulator protein Notch1 advances the cell cycle. Activation of Notch1 induced the production of a protein that chops up cell cycle inhibitors, leading to a shortened G1 phase and a faster transition into S phase (but no overall increase in proliferation).
Sarmento et al. now find the link and show that constitutive Notch1 activation drives cell cycling by increasing the activity of cyclin-dependent kinase-2 (CDK2), a protein that promotes progression into the S phase of the cell cycle. CDK2 activation resulted from the degradation of the CDK inhibitor protein p27kip1, which was triggered by the Notch1-induced expression of a protein called SKP2—a component of a ubiquitin ligase complex that targets proteins for proteosomal degradation.
How Notch-induced changes in cell cycle kinetics influence differentiation programs is not completely clear. The authors suggest that a shortened G1 phase—during which cells are thought to be most responsive to fate-deciding differentiation signals—may minimize the window of differentiation opportunity and thus help maintain the progenitor cell pool.