In blast cells obtained from patients with acute myelogenous leukemia,
p53 mRNA was present in all the samples examined while the expression
of p53 protein was;as variable from patient to patient, Mutations in
the p53 gene are infrequent in this disease and, hence, variable prote
in expression in the majority of the samples cannot be accounted for b
y mutation, In this study, we examined the regulation of p53 gene expr
ession in human leukemic blasts and characterized the p53 transcripts
in these cells, We found control both at the level of RNA abundance an
d at the level of translation, Four experiments point towards translat
ional control of human p53 gene expression, First, there is no correla
tion between the level of p53 mRNA and the level of p53 protein expres
sion in blast cells, Second, in two cell lines with similar levels of
p53 protein expression but with different levels of p53 mRNA, we find
that there is preferential association of p53 mRNA with large polysome
s in the cells with less p53 RNA, Third, translation of synthetic huma
n p53 transcripts in cell-free extracts is inhibited by the p53 3'UTR,
Fourth, the p53 3'UTR, when present in cis, can repress translation o
f a heterologous transcript, These observations raise the possibility
that human p53 mRNA translation may be regulated in vivo by RNA bindin
g factors acting on the p53 3'UTR.