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p73 is a simian [correction of human] p53-related protein that can induce apoptosis
C A Jost1, M C Marin, W G Kaelin
1Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.
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).
Insights
The newly identified p73 protein shares similarities with the tumor suppressor p53. Overexpressed p73 can inhibit cell growth and induce apoptosis, similar to p53.
Area of Science:
- Molecular Biology
- Cancer Genetics
Background:
- The p53 protein is a critical tumor suppressor frequently mutated in human cancers.
- p53's function involves DNA binding to regulate target genes like p21Waf1/Cip1, inhibiting cell growth.
Purpose of the Study:
- To investigate the function of a newly identified gene, p73, which encodes a protein with significant sequence similarity to p53.
- To determine if p73 exhibits p53-like tumor suppressor activities.
Main Methods:
- Sequence analysis to identify conserved p53 DNA-binding residues in p73.
- Functional assays to assess p73's transcriptional activity on p53-responsive genes.
- Cell growth inhibition and apoptosis induction assays.
Main Results:
- The p73 protein conserves key p53 residues essential for DNA binding.
- Overproduction of p73 activates transcription of p53-responsive genes.
- p73 inhibits cell growth and induces apoptosis in a manner similar to p53.
Conclusions:
- The p73 gene, located on chromosome 1 in a region frequently deleted in neuroblastomas, encodes a functional protein with p53-like tumor suppressor activities.
- p73 represents a novel player in cancer biology with potential implications for tumor suppression.