Human p53 protein was found to be functional in fission yeast in terms of g
rowth repression and checkpoint control. Expression of wild-type p53 or the
hut spot mutant p53(His273) results in dramatic motphological changes and
loss of viability of recipient yeast cells. Overexpression of cdc25C phosph
atase, the mitotic activator of cdc2, results in suppression of a p53-induc
ed growth arrest. In order to understand the interplay between p53 and cdc2
5C in mammalian cells we isolated and sequenced cdc25C cDNA from the epider
moid carcinoma cell line A431, which is known to carry the P53(His273) muta
tion. Two different ent transcripts of the human cdc25C gene were detected
by RT-PCR analysis - one full-length transcript and a shortened version (cd
c25Cdm) that carries two deletions in the 5'-region of the gene. In normal
human skin fibroblasts only one full-length cdc25C transcript was detected.
The two different transcripts code fur proteins with a molecular weight of
55 kDa and 46 kDa, respectively. Both cdc25C cDNAs from A431 cells were fo
und to complement A conditional lethal cdc25.22 mutant strain ain as well a
s a cdc25 deletion strain of Schizosaccharomyces pombe indicating that func
tional proteins were translated. Expression of cdc25Cdm variant leads to a
stronger uncoupling of DNA replication from mitosis than expression of cdc2
5C suggesting that the deletion within the amino-terminus of cdc25C leads t
o a protein which might contribute some potential fur oncogenic transformat
ion, As with cdc25C, uncoupling of the DNA synthesis checkpoint by cdc25Cdm
was reversed by coexpression of wild-type p53.