Abstract
The protein p53 is the most frequently mutated tumour suppressor to be identified so far in human cancers. The ability of p53 to inhibit cell growth is due, at least in part, to its ability to bind to specific DNA sequences and activate the transcription of target genes such as that encoding the cell-cycle inhibitor p21Waf1/Cip1 . A gene has recently been identified that is predicted to encode a protein with significant amino-acid sequence similarity to p53. In particular, each of the p53 amino-acid residues implicated in direct sequence-specific DNA binding is conserved in this protein. This gene, called p73, maps to the short arm of chromosome 1, and is found in a region that is frequently deleted in neuroblastomas. Here we show that p73 can, at least when overproduced, activate the transcription of p53-responsive genes and inhibit cell growth in a p53-like manner by inducing apoptosis (programmed cell death).
MeSH terms
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Apoptosis*
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Cell Division / genetics
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Cell Division / physiology
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Cell Line
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Chloramphenicol O-Acetyltransferase / genetics
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Chromosome Mapping
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Chromosomes, Human, Pair 1
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Genes, Tumor Suppressor*
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Growth Inhibitors / genetics
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Growth Inhibitors / physiology
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Humans
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Molecular Sequence Data
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Mutagenesis, Site-Directed
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Neuroblastoma / genetics
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Plasmids
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Transcriptional Activation
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Tumor Cells, Cultured
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Tumor Protein p73
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Tumor Suppressor Protein p53* / chemistry
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Tumor Suppressor Protein p53* / genetics
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Tumor Suppressor Protein p53* / physiology
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Tumor Suppressor Proteins
Substances
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA-Binding Proteins
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Growth Inhibitors
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Nuclear Proteins
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TP73 protein, human
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Tumor Protein p73
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Tumor Suppressor Protein p53
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Tumor Suppressor Proteins
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Chloramphenicol O-Acetyltransferase