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Updated: May 9, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Transactivation specificity is conserved among p53 family proteins and depends on a response element sequence code
Yari Ciribilli1, Paola Monti, Alessandra Bisio
1Laboratory of Transcriptional Networks, Centre for Integrative Biology (CIBIO), University of Trento, TN, 38060 Italy, Molecular Mutagenesis and DNA Repair Unit, IRCSS Azienda Ospedaliera Universitaria San Martino-IST-Istituto Nazionale per la Ricerca sul Cancro, Genoa 16132, Italy, Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093, USA and Chromosome Stability Group, Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, NIEHS, NIH, RTP, NC, 27709, USA.
p53 family proteins, including p73, p63, and p53, share similar DNA binding and transactivation profiles. Mutations in conserved amino acids fine-tune this activity, revealing a DNA response element code that predicts gene transactivation, particularly for apoptosis-related genes.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- The p53 family of proteins (p53, p63, p73) are crucial transcription factors involved in cell cycle regulation, DNA repair, and apoptosis.
- Previous studies indicated structural similarities in DNA recognition among p53 family members.
Purpose of the Study:
- To investigate the functional overlap in transactivation activity among p53 family proteins.
- To identify specific DNA response elements (REs) and protein mutations that modulate transactivation potential.
- To uncover a potential code governing RE-transactivation specificity.
Main Methods:
- Assessed transactivation activity of p53 family proteins across numerous REs using yeast and human cell line assays.
- Introduced mutations at conserved amino acids within the DNA-binding domain (loops L1 and L3).
- Analyzed DNA-binding cooperativity in vitro and protein-DNA complex structures.
- Correlated RE sequence variations with transactivation specificity.
Main Results:
- Demonstrated overlapping transactivation profiles for p53, p63, and p73.
- Identified specific mutations (e.g., S139F in p73) that enhance transactivation potential and DNA-binding cooperativity.
- Discovered a RE-transactivation code predicting enhanced activity, with a stronger correlation for apoptosis-associated gene promoters.
- Observed structural flexibility in loop L1 associated with enhanced transactivation.
Conclusions:
- p53 family proteins exhibit functionally overlapping transactivation capabilities.
- Modifications in conserved DNA-binding domain regions can precisely tune transactivation.
- A sequence-specific code dictates RE-transactivation, offering insights into gene regulation, especially in apoptosis pathways.
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