N-Myc is a member of the myc family of proto-oncogenes involved in initiati
on and progression of tumors. While c-MYC, the most characterized member of
the family, is well known for its role in cellular proliferation and apopt
osis, the function of N-MYC in differentiation and proliferation remains un
clear. N-Myc mutant mice present a phenotype more consistent with a role of
N-MYC protein in proliferation of precursor populations than in differenti
ation per se. Recent studies have also shown that N-MYC can enhance apoptos
is and shorten the G(1) phase of the cell cycle. However, the role of N-MYC
in instigating cell-cycle progression has not been clearly demonstrated. H
ere, we demonstrate that overexpression of N-myc or activation of inducible
N-MYC proteins is sufficient to induce apoptosis in serum-starved fibrobla
st cells, an effect that can be counteracted by overexpression of Bcl-2. Mo
reover, 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 ro
les during embryonic development are mediated, at least in part, via their
specific profile of expression rather than by their different protein funct
ions.