Figure 2.

Apoptosis pathways mediated by MYC and MYC cofactors. Overexpressed or deregulated MYC (oncogenic MYC) induces ARF protein levels. ARF can then bind to inactivate MDM2, causing p53 induction, or bind to MYC to induce EGR1 through noncanonical transactivation while inhibiting canonical transactivation or bind to MIZ-1 and MYC to cause repression of BCL2. ARF-independent apoptosis can occur through DNA damage. The relative binding and regulation of ARF to its many partners is unknown. These pathways have primarily been investigated in fibroblasts. ARF and MIZ-1 are shown in red as MYC cofactors.