MYC needs MNT

MYC family members c-MYC, N-MYC and L-MYC are amplified, translocated and otherwise deregulated in numerous and diverse tumor types. These events, which typically lead to constitutively increased MYC, provide a proliferative advantage to cells by boosting anabolic metabolism and supporting cell cycle progression. However, the proliferative response to excessive MYC is countered in many cell types by increased apoptosis, and a number of studies have shown that events that inhibit MYC-driven apoptosis strongly cooperate with MYC in driving oncogenesis. High-level MYC expression, such as that found in many tumors, does occur normally in cells, but this typically happens only transiently in the context of growth factor-induced cell cycle entry. Cells are spared the proapoptotic effects of Myc in this setting, because mitogenic growth factors also stimulate prosurvival signaling. Thus the apoptotic response to ectopic MYC likely results from a decoupling of increased MYC from prosurvival signaling needed for productive cell cycle entry and progression. But what are the key prosurvival factors and events that normally protect cells from the transient burst of MYC during cell cycle entry, and how might these events impinge on MYCdriven oncogenesis? One factor that appears to protect cells from MYC-provoked apoptosis is MNT. MNT shares with MYC a related basic-helix-loop-helix domain that mediates dimerization with MAX and DNA binding at E-box sequences, but MNT and MYC have opposing transcriptional activity. Consistent with MNT functioning as a MYC antagonist, ectopic MNT expression can interfere with MYCdependent transcription activation as well as proliferation and transformation MYC needs MNT