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Updated: May 10, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Eukaryotic translation elongation factor 1-alpha 1 inhibits p53 and p73 dependent apoptosis and chemotherapy
Alvaro Blanch1, Fiona Robinson, Ian R Watson
1Department of Paediatrics and Cell Biology Program, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Abstract:
The p53 family of transcription factors is a key regulator of cell proliferation and death. In this report we identify the eukaryotic translation elongation factor 1-alpha 1 (eEF1A1) to be a novel p53 and p73 interacting protein. Previous studies have demonstrated that eEF1A1 has translation-independent roles in cancer. We report that overexpression of eEF1A1 specifically inhibits p53-, p73- and chemotherapy-induced apoptosis resulting in chemoresistance. Short-interfering RNA-mediated silencing of eEF1A1 increases chemosensitivity in cell lines bearing wild type p53, but not in p53 null cells. Furthermore, silencing of eEF1A1 partially rescues the chemoresistance observed in response to p53 or p73 knockdown, suggesting that eEF1A1 is a negative regulator of the pro-apoptotic function of p53 and p73. Thus, in the context of p53-family signaling, eEF1A1 has anti-apoptotic properties. These findings identify a novel mechanism of regulation of the p53 family of proteins by eEF1A1 providing additional insight into potential targets to sensitize tumors to chemotherapy.
Insights
Eukaryotic translation elongation factor 1-alpha 1 (eEF1A1) interacts with p53 and p73, inhibiting apoptosis and causing chemoresistance. Silencing eEF1A1 enhances chemotherapy sensitivity, revealing a new target for cancer treatment.
Area of Science:
- Molecular Biology
- Cancer Biology
- Cell Death Pathways
Background:
- The p53 family of transcription factors are critical regulators of cell proliferation and apoptosis.
- Eukaryotic translation elongation factor 1-alpha 1 (eEF1A1) has known roles in translation and emerging translation-independent functions in cancer.
Purpose of the Study:
- To identify novel interacting proteins of the p53 family.
- To investigate the role of eEF1A1 in p53- and p73-mediated apoptosis and chemoresistance.
Main Methods:
- Co-immunoprecipitation to identify protein interactions.
- Overexpression and short-interfering RNA (siRNA) silencing of eEF1A1 in cancer cell lines.
- Assessment of apoptosis induction and chemosensitivity.
- Analysis of p53 and p73 activity.
Main Results:
- eEF1A1 was identified as a novel interacting protein of p53 and p73.
- Overexpression of eEF1A1 inhibited p53-, p73-, and chemotherapy-induced apoptosis, leading to chemoresistance.
- Silencing eEF1A1 increased chemosensitivity in cells with wild-type p53 but not in p53-null cells.
- eEF1A1 silencing partially rescued chemoresistance in p53 or p73 knockdown cells, indicating eEF1A1 is a negative regulator of p53/p73 pro-apoptotic functions.
Conclusions:
- eEF1A1 possesses anti-apoptotic properties within the context of p53-family signaling.
- eEF1A1 represents a novel mechanism regulating p53 family proteins.
- Targeting eEF1A1 could sensitize tumors to chemotherapy by modulating p53-family-mediated apoptosis.
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