Mechanisms for escaping c-MYC induced apoptosis. Panels A–C are adapted from Dang et al.28 (A) Acute activation of Myc induces target genes involved in proliferation, but the activation of ARF, p53, and Bim (which inhibits Bcl2) leads to apoptosis or cell cycle arrest. Activation of both the ARF/p53 and Bim pathways are required for apoptosis induction (B) Chronic expression of wild-type Myc induces lymphomagenesis coordinately with the inactivation of ARF or p53. (C) Chronic expression of Myc mutants derived from Burkitt lymphoma (BL) cells fail to activate Bim and hence promote lymphomagenesis despite the presence of wild-type p53 or ARF. (D) In our proposed model, EBV in a Wp-restricted form of latency down regulates Bim in BL cells and thus contributes to lymphomagenesis.
