Model of the autoregulatory VRK1-p53-Hdm2-DRAM loop.

Several types of DNA damage mechanisms can induce VRK1, stabilizing and activating p53-dependent transcription (black line). Among the p53-induced genes, Hdm2 promotes p53 degradation via ubiquitylation (blue line), and DRAM induces VRK1 degradation in the lysosome (red line). VRK1 and DRAM are in the same late endosomal vesicle that fuses to lysosomes, but do not interact directly. PP: unknown phosphatase.