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Updated: Aug 8, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p19ras brings a new twist to the regulation of p73 by Mdm2
Kelly Lynn Harms1, Xinbin Chen
1Department of Cell Biology, University of Alabama, Birmingham, AL 35294, USA.
Abstract:
p53 is the most commonly mutated gene in human cancer. It is now known that the p53 family proteins p63 and p73 play important roles in tumor suppression as well as in development. Because p63 and p73 are rarely mutated in human cancer, understanding the signaling pathways that activate p63 and p73 will not only shed light on the developmental processes regulated by p63 and p73 but may also yield insight into ways to harness p63 and p73 activity for cancer therapy. Recent research has shown that an alternative splice form of c-H-ras, called p19ras, is a positive regulator of p73beta through a mechanism that involves the E3 ubiquitin ligase Mdm2. Implications for this previously unidentified means of regulation are discussed in light of tumor suppression and are extended to p53 and p63.
Insights
The p53 family proteins p63 and p73 are crucial for tumor suppression. A newly identified pathway involving p19ras and Mdm2 activates p73beta, offering potential cancer therapy strategies.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The p53 gene is frequently mutated in human cancers.
- p53 family proteins, p63 and p73, are vital for tumor suppression and development.
- p63 and p73 mutations are rare in human cancers, suggesting regulation by signaling pathways.
Purpose of the Study:
- To investigate signaling pathways that activate p63 and p73.
- To explore the role of these pathways in development and cancer therapy.
- To understand the function of p19ras and Mdm2 in regulating p73beta.
Main Methods:
- Analysis of alternative splicing of c-H-ras.
- Investigation of the interaction between p19ras, Mdm2, and p73beta.
- Exploration of the E3 ubiquitin ligase activity of Mdm2.
Main Results:
- An alternative splice form of c-H-ras, p19ras, positively regulates p73beta.
- This regulation occurs via a mechanism involving the E3 ubiquitin ligase Mdm2.
- This represents a previously unidentified regulatory pathway.
Conclusions:
- The p19ras-Mdm2 pathway is a novel regulator of p73beta.
- Understanding this pathway offers insights into developmental processes.
- This pathway may provide new targets for cancer therapy by harnessing p73 activity.
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