ArticleMolecular and cellular biology2002
Transcriptional regulation of the mdm2 oncogene by p53 requires TRRAP acetyltransferase complexes.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 111 citations in OpenAlex.
- Divergent SAGA complexes shape the Toxoplasma transcriptome for lytic cycle progression and host interaction.Nature communications · 2026Article
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Structural insights into the human NuA4/TIP60 acetyltransferase and chromatin remodeling complex.Science (New York, N.Y.) · 2024Article
- Cancer-specific association between Tau (MAPT) and cellular pathways, clinical outcome, and drug response.Scientific data · 2023Article
- TRRAP Enhances Cancer Stem Cell Characteristics by Regulating NANOG Protein Stability in Colon Cancer Cells.International journal of molecular sciences · 2023Article
- The chromatin remodeling factors EP300 and TRRAP are novel SMYD3 interactors involved in the emerging 'nonmutational epigenetic reprogramming' cancer hallmark.Computational and structural biotechnology journal · 2023Article
- The TRRAP transcription cofactor represses interferon-stimulated genes in colorectal cancer cells.eLife · 2022Article
- Structure of the human SAGA coactivator complex.Nature structural & molecular biology · 2021Article
- Beyond HAT Adaptor: TRRAP Liaisons with Sp1-Mediated Transcription.International journal of molecular sciences · 2021Review
- What do Transcription Factors Interact With?Journal of molecular biology · 2021Review
- The Diarylheptanoid Curcumin Induces MYC Inhibition and Cross-Links This Oncoprotein to the Coactivator TRRAP.Frontiers in oncology · 2021Article
- Estrogen receptor alpha (ERα)-mediated coregulator binding and gene expression discriminates the toxic ERα agonist diethylstilbestrol (DES) from the endogenous ERα agonist 17β-estradiol (E2).Cell biology and toxicology · 2020Article
- Association of Mouse Double Minute 2 -309T>G Polymorphism with Acute Myeloid Leukemia in an Iranian Population: A Case- Control Study.Asian Pacific journal of cancer prevention : APJCP · 2019Article
- Share and share alike: the role of Tra1 from the SAGA and NuA4 coactivator complexes.Transcription · 2019Review
- Formation of a structurally-stable conformation by the intrinsically disordered MYC:TRRAP complex.PloS one · 2019Article
- Characterization and Molecular Mechanism of Peptide-Conjugated Gold Nanoparticle Inhibiting p53-HDM2 Interaction in Retinoblastoma.Molecular therapy. Nucleic acids · 2017Article
- Cryo-EM structure of the SAGA and NuA4 coactivator subunit Tra1 at 3.7 angstrom resolution.eLife · 2017Article
- Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy.Molecular therapy oncolytics · 2017Review
- SGF29 and Sry pathway in hepatocarcinogenesis.World journal of biological chemistry · 2015Review
- Systematic identification of cancer driving signaling pathways based on mutual exclusivity of genomic alterations.Genome biology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The p53 tumor suppressor regulates the cellular response to genetic damage through its function as a sequence-specific transcription factor. Among the most well-characterized transcriptional targets of p53 is the mdm2 oncogene. Activation of mdm2 is critical in the p53 pathway because the mdm2 protein marks p53 for proteosome-mediated degradation, thereby providing a negative-feedback loop. Here we show that the ATM-related TRRAP protein functionally cooperates with p53 to activate mdm2 transcription. TRRAP is a component of several multiprotein acetyltransferase complexes implicated in both transcriptional regulation and DNA repair. In support of a role for these complexes in mdm2 expression, we show that transactivation of the mdm2 gene is augmented by pharmacological inhibition of cellular deacetylases. In vitro analysis demonstrates that p53 directly binds to a TRRAP domain previously shown to be an activator docking site. Furthermore, transfection of cells with antisense TRRAP blocks p53-dependent transcription of mdm2. Finally, using chromatin immunoprecipitation, we demonstrate direct p53-dependent recruitment of TRRAP to the mdm2 promoter, followed by increased histone acetylation. These findings suggest a model in which p53 directly recruits a TRRAP/acetyltransferase complex to the mdm2 gene to activate transcription. In addition, this study defines a novel biochemical mechanism utilized by the p53 tumor suppressor to regulate gene expression.
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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.