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Updated: Jun 22, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Interaction between the transactivation domain of p53 and PC4 exemplifies acidic activation domains as
Sridharan Rajagopalan1, Antonina Andreeva, Daniel P Teufel
1MRC Centre for Protein Engineering, Cambridge, United Kingdom.
Abstract:
The tumor suppressor p53 regulates cell cycle arrest and apoptosis by transactivating several genes that are critical for these processes. The transcriptional activity of p53 is often regulated by post-translational modifications and its interactions with various transcriptional coactivators. Here we report a physical interaction between the N-terminal transactivation domain (TAD) of p53 and the C-terminal DNA-binding domain of positive cofactor 4 (PC4(CTD)). Using NMR spectroscopy, we showed that residues 35-57 (TAD2) interact with PC4. (15)N,(1)H HSQC and fluorescence competition experiments indicated that TAD binds to the DNA-binding site of PC4. Hepta-phosphorylation of the TAD peptide increased its binding affinity. Computer modeling of the p53N-PC4 complex revealed several important interactions that are reminiscent of those in the single-stranded DNA-PC4 complex. The ubiquitous nature of the acidic transactivation domain of p53 in mediating interactions with several transcription cofactors is also manifested as a DNA mimetic.
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