Aj. Wagner et al., MYC-MEDIATED APOPTOSIS REQUIRES WILD-TYPE P53 IN A MANNER INDEPENDENTOF CELL-CYCLE ARREST AND THE ABILITY OF P53 TO INDUCE P21(WAF1 CIP1)/, Genes & development, 8(23), 1994, pp. 2817-2830
Deregulated expression of the c-myc proto-oncogene can lead to apoptos
is under certain physiological conditions. By introducing a conditiona
lly active Myc allele into primary embryo fibroblasts null for p53, an
d into fibroblasts without endogenous p53 expression but ectopically e
xpressing a temperature-sensitive p53 allele, we show that expression
of wild-type p53 is required for susceptibility to Myc-mediated apopto
sis. Although ectopic expression of wild-type p53 blocked cells in the
G(1) phase of the cell cycle, G(1) arrest by isoleucine starvation, i
n a manner independent of p53, did not confer susceptibility to apopto
sis. Thus, growth arrest per se is not sufficient to induce Myc-mediat
ed apoptosis; instead, a property intrinsic to p53 is specifically req
uired. Moreover, apoptosis did not require induction of p53 target pro
teins, including the cyclin-dependent kinase inhibitor p21(waf1/cip1).
Therefore, the role of p53 in apoptosis may be distinct from its role
in cell cycle arrest.