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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
The emerging p53 gene family
1Howard Hughes Medical Institute and Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA. william_kaelin@dfci.harvard.edu
Abstract:
Perturbation of p53 protein function is a common, if not universal, finding in human cancer. Tumor suppression by p53 is due, at least in part, to its ability to activate transcription of certain genes involved in cell cycle control and apoptosis (programmed cell death). Two additional members of the mammalian p53 family, p73 and p51, which is also known as p40, p63, KET, or p73L, were recently identified. Both of these proteins share substantial sequence homology with p53 and can, at least when overproduced, activate p53-responsive promoters and induce apoptosis. Nonetheless, data on differences between these proteins and p53 are emerging. For example, p73 is not induced by DNA damage and is not targeted for inactivation by viral oncoproteins such as simian virus 40 (SV40) T antigen, adenovirus E1B 55K, and human papillomavirus E6. In contrast to p53, neither p73 nor p51 appears to be frequently mutated in human cancers on the basis of the limited studies reported to date. Finally, unlike p53, cells produce multiple p73 and p51 isoforms as a result of alternative splicing, and production of p73 and p51 appears to be restricted to certain tissues. Additional studies are required to determine the role, if any, that p73 and p51 play in cell growth control and carcinogenesis.
Insights
The p53 protein family, including p73 and p51, plays a role in tumor suppression. Unlike p53, p73 and p51 are not frequently mutated in cancers and have distinct regulatory mechanisms.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- p53 protein is crucial for tumor suppression by regulating cell cycle and apoptosis.
- Two related proteins, p73 and p51 (also known as p40, p63, KET, or p73L), share homology with p53.
- These family members can activate p53-responsive promoters and induce apoptosis when overproduced.
Purpose of the Study:
- To explore the differences between p53, p73, and p51.
- To investigate the potential roles of p73 and p51 in cell growth control and carcinogenesis.
- To understand the unique characteristics of p73 and p51 compared to p53.
Main Methods:
- Comparative analysis of protein function and regulation.
- Examination of gene activation and apoptosis induction.
- Review of mutation frequencies in human cancers.
- Investigation of protein isoform production and tissue-specific expression.
Main Results:
- p73 is not induced by DNA damage and evades inactivation by viral oncoproteins.
- p73 and p51 do not appear to be frequently mutated in human cancers.
- Cells produce multiple isoforms of p73 and p51 through alternative splicing.
- p73 and p51 expression is restricted to certain tissues.
Conclusions:
- p73 and p51 exhibit distinct properties compared to p53, particularly in their regulation and mutation status.
- The differential expression and isoform production suggest specialized roles for p73 and p51.
- Further research is needed to fully elucidate the functions of p73 and p51 in cancer development and prevention.
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