ArticleThe Journal of biological chemistry2009
Interaction between the transactivation domain of p53 and PC4 exemplifies acidic activation domains as single-stranded DNA mimics.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- The disordered p53 transactivation domain is the target of FOXO4 and the senolytic compound FOXO4-DRI.Nature communications · 2025Article
- Human PC4 supports telomere stability and viability in cells utilizing the alternative lengthening of telomeres mechanism.EMBO reports · 2024Article
- BANF1 promotes glutamate-induced apoptosis of HT-22 hippocampal neurons.Molecular biology reports · 2023Article
- Dynamic structures of intrinsically disordered proteins related to the general transcription factor TFIIH, nucleosomes, and histone chaperones.Biophysical reviews · 2022Review
- Peptide and protein chemistry approaches to study the tumor suppressor protein p53.Organic & biomolecular chemistry · 2022Review
- A phosphorylation-dependent switch in the disordered p53 transactivation domain regulates DNA binding.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Tumor-Suppressor p53TADChembiochem : a European journal of chemical biology · 2020Article
- Long-range regulation of p53 DNA binding by its intrinsically disordered N-terminal transactivation domain.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Structural Basis for the Interaction between p53 Transactivation Domain and the Mediator Subunit MED25.Molecules (Basel, Switzerland) · 2018Article
- Inhibition of PC4 radiosensitizes non-small cell lung cancer by transcriptionally suppressing XLF.Cancer medicine · 2018Article
- Selective targeting p53Oncogene · 2017Article
- A biochemical and biophysical model of G-quadruplex DNA recognition by positive coactivator of transcription 4.The Journal of biological chemistry · 2017Article
- The Transactivation Domains of the p53 Protein.Cold Spring Harbor perspectives in medicine · 2017Review
- Nuclear Localization Signal and p53 Binding Site in MAP/ERK Kinase Kinase 1 (MEKK1).Journal of cellular biochemistry · 2015Article
- Peptides derived from the dependence receptor ALK are proapoptotic for ALK-positive tumors.Cell death & disease · 2015Article
- PC4 induces lymphangiogenesis dependent VEGF-C/VEGF-D/VEGFR-3 axis activation in lung adenocarcinoma.American journal of cancer research · 2015Article
- Pathological unfoldomics of uncontrolled chaos: intrinsically disordered proteins and human diseases.Chemical reviews · 2014Review
- Dual-site interactions of p53 protein transactivation domain with anti-apoptotic Bcl-2 family proteins reveal a highly convergent mechanism of divergent p53 pathways.The Journal of biological chemistry · 2013Article
- On the binding affinity of macromolecular interactions: daring to ask why proteins interact.Journal of the Royal Society, Interface · 2013Review
- A small molecule directly inhibits the p53 transactivation domain from binding to replication protein A.Nucleic acids research · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.