Figure 7.

Model for cell-cycle regulation of LIN-12 NOTCH signaling. During the G1 phase of the cell cycle, LIN-12 NOTCH is cleaved upon binding to a DSL ligand, thereby releasing the NICD fragment that activates transcription of target genes. Alternatively, NOTCH can undergo endocytosis followed by lysosomal degradation. The activity of the G1-specific CDK-4/CYD-1 and CDK-2/CYE-1 complexes positively regulate LIN-12 NOTCH signaling in P5.p, P6.p, and P7.p by stabilizing full-length NOTCH at the apical plasma membrane and NICD in the nucleus, respectively. Degradation of NICD in P6.p occurs during the G2 phase, when activation of the G2-specific CDK-1/CYB-3 complex terminates NOTCH signaling by inducing ubiquitin-mediated proteasomal degradation of NICD.