Figure 1.

ARF–Mdm2–p53 circuitry. Myc rapidly induces p19^ARF expression, but without evidence that Myc transactivates the ARF promoter, its action may be indirect. p19^ARF binds directly with Mdm2 to neutralize its function and triggers p53-dependent transcription. In turn, Mdm2 is a p53-responsive gene (pathway A) whose activation cancels the p53 response. Through ill-defined mechanisms, p53 regulates negatively both ARF (pathway B) and Myc (pathway C). However, it is conceivable that the feedback loops affecting ARF and Myc are one and the same.