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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
SirT1 fails to affect p53-mediated biological functions
Christopher Kamel1, Meena Abrol, Karen Jardine
1Ottawa Health Research Institute and Departments of Medicine and Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada K1H 8L6.
Aging Cell
|January 31, 2006
Summary
SirT1 protein deacetylase activity does not significantly impact p53 gene transcription or radiation-induced apoptosis. SirT1-null mice lacking p53 still exhibit developmental defects and perinatal lethality, indicating p53 is not the cause.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- The SirT1 gene encodes a protein deacetylase.
- p53 is a known SirT1 substrate, with SirT1-dependent deacetylation reported to negatively regulate p53's transcriptional activity.
Purpose of the Study:
- To investigate if p53 hyperactivity causes developmental defects and perinatal lethality in SirT1-null mice.
- To re-examine the role of SirT1 in modulating p53 activity.
Main Methods:
- Created mice deficient for both SirT1 and p53.
- Assessed developmental phenotypes and survival rates.
- Examined SirT1's effect on p53-dependent transcription of genes.
- Evaluated sensitivity of thymocytes and splenocytes to radiation-induced apoptosis.
Main Results:
- Mice lacking both SirT1 and p53 showed developmental defects and perinatal lethality, similar to SirT1-deficient mice.
- SirT1 interacts with p53 but has minimal impact on p53-dependent gene transcription.
- SirT1 did not alter the sensitivity of lymphocytes to radiation-induced apoptosis.
Conclusions:
- p53 hyperactivity is not the cause of developmental defects and perinatal lethality in SirT1-null mice.
- SirT1 does not significantly modulate many p53-mediated biological activities, despite p53 being a SirT1 substrate.
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