N-Myc Shares Cellular Functions with c-Myc

Abstract

N- Myc is a member of the myc family of proto-oncogenes involved in initiation and progression of tumors. While c-MYC, the most characterized member of the family, is well known for its role in cellular proliferation and apoptosis, the function of N-MYC in differentiation and proliferation remains unclear. N- Myc mutant mice present a phenotype more consistent with a role of N-MYC protein in proliferation of precursor populations than in differentiation per se . Recent studies have also shown that N-MYC can enhance apoptosis and shorten the G₁ phase of the cell cycle. However, the role of N-MYC in instigating cell-cycle progression has not been clearly demonstrated. Here, we demonstrate that overexpression of N- myc or activation of inducible N-MYC proteins is sufficient to induce apoptosis in serum-starved fibroblast cells, an effect that can be counteracted by overexpression of Bcl-2 . Moreover, N-MYC can induce the reentry of quiescent cells into the cell cycle even in the absence of external stimuli. These results indicate that N-MYC and c-MYC share many properties, supporting the model that MYC-specific roles during embryonic development are mediated, at least in part, via their specific profile of expression rather than by their different protein functions.