Gadd45 mutations are uncommon in human tumour cell lines

GADD45 is an evolutionarily conserved gene that encodes a small acidic, nuc lear protein and is an example of a p53 responsive gene. Gadd45 protein has been shown to interact with PCNA and also p21(waf1). It has been implicate d in growth arrest, DNA repair, chromatin structure and signal transduction , The confusing biochemical data has been clarified by the demonstration th at Gadd45 null mice have a phenotype strikingly similar to that of p53 null mice, being tumour prone and showing marked genomic instability. We have t ested the hypothesis that mutations in the GADD45 coding region might subst itute for p53 abnormalities in tumour cell lines where p53 is wild type. Af ter generating cDNA from mRNA in a panel of 24 cell lines we sequenced the GADD45 cDNA and have demonstrated that no mutations can be observed, even i n the p53 wild type cell lines. Such data suggest that Gadd45 mutations are uncommon in human cancer. From this we postulate that, despite the phenoty pe of the GADD45 null mouse, GADD45 is unlikely to be the key mechanistic d eterminant of the tumour suppressor activity of the p53 pathway.