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The p53 gene family
1Howard Hughes Medical Institute and Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, MA 02115, USA. william_kaelin@dfci.harvard.edu
Oncogene
|January 5, 2000
Summary
p73 and p63 proteins are p53 homologs that rarely mutate in cancer. Evidence does not firmly support p73 and p63 as tumor suppressors, despite earlier hypotheses.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- p73 and p63 are homologous to p53, capable of binding p53 DNA sites and inducing apoptosis.
- Unlike p53, p73 and p63 genes exhibit complex alternative splicing, producing diverse protein isoforms.
- p73 and p63 are infrequently mutated in human cancers, unlike p53.
Purpose of the Study:
- To evaluate the role of p73 and p63 in cancer, specifically addressing their tumor suppressor potential.
- To critically assess the hypothesis that p73 monoallelic expression contributes to carcinogenesis.
Main Methods:
- Comparative analysis of p53, p73, and p63 protein functions.
- Review of mutation data in human cancers for p53, p73, and p63.
- Examination of p73 expression levels and allelic variation in tumor samples.
Main Results:
- p73 and p63 can activate p53-responsive genes and induce apoptosis when overproduced.
- p63 alternative splicing generates proteins with distinct biological activities.
- p73 and p63 are rarely mutated in cancer, and p73 inactivation is not essential for viral transformation.
- p73 mRNA levels are often elevated in tumors, not decreased.
- Inter- and intra-individual variations exist in p73 monoallelic expression.
Conclusions:
- Current evidence does not establish p73 and p63 as tumor suppressors.
- The proposed link between p73 monoallelic expression and carcinogenesis requires cautious interpretation due to expression variability and increased mRNA levels in tumors.