A human tumour-derived mutant p53 protein induces a p34cdc2 reversible growth arrest in fission yeast.
We have expressed wild-type and human tumour-derived mutant p53 cDNA genes in the fission yeast Schizosaccharomyces pombe. In the case of one mutant this resulted in a growth arrest of recipient yeast cells. In contrast, wild-type p53 and three other mutant proteins tested did not block outgrowth of colonies. Human and yeast cdc2 acted as functionally equivalent extragenic suppressors of the mutant-induced growth arrest allowing the establishment of viable p53 expressor strains. In cotransformation assays the mutant allele was found to be dominant over wt p53. Our results provide the first evidence of a functional relationship between p53 and p34cdc2 in an in-vivo system and suggest that the wide variety of mutant proteins present in human tumours may fall into functionally distinct subclasses.
Cell Proliferation Laboratory, Marie Curie Cancer Research Institute, Oxted, Surrey, UK.
P
P
Wagner
V
V
Simanis
T
T
Maimets
E
E
Keenan
C
C
Addison
R
R
Brain
M
M
Grimaldi
H W
HW
Sturzbecher
J
J
Jenkins
D015152:Blotting, Northern; D016203:CDC2 Protein Kinase / Q000235:genetics* / Q000378:metabolism; D002455:Cell Division; D003001:Cloning, Molecular; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D016296:Mutagenesis; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics* / Q000254:growth & development; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D016203:CDC2 Protein Kinase