Gadd45 mutations are uncommon in human tumour cell lines.
GADD45 is an evolutionarily conserved gene that encodes a small acidic, nuclear protein and is an example of a p53 responsive gene. Gadd45 protein has been shown to interact with PCNA and also p21waf1. It has been implicated in growth arrest, DNA repair, chromatin structure and signal transduction. The confusing biochemical data has been clarified by the demonstration that Gadd45 null mice have a phenotype strikingly similar to that of p53 null mice, being tumour prone and showing marked genomic instability. We have tested the hypothesis that mutations in the GADD45 coding region might substitute for p53 abnormalities in tumour cell lines where p53 is wild type. After 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 in the p53 wild type cell lines. Such data suggest that Gadd45 mutations are uncommon in human cancer. From this we postulate that, despite the phenotype of the GADD45 null mouse, GADD45 is unlikely to be the key mechanistic determinant of the tumour suppressor activity of the p53 pathway.
Campomenosi
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P
Laboratory of Mutagenesis, National Institute for Cancer research, Genova, Italy.
Hall
P A
PA
D000818:Animals; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D000097642:GADD45 Proteins
D018076:DNA, Complementary; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D000097642:GADD45 Proteins