Evidence map›Paper›PMID 17438265›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2007

Four domains of p300 each bind tightly to a sequence spanning both transactivation subdomains of p53.

Daniel P Teufel, Stefan M Freund, Mark Bycroft, Alan R Fersht

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed
6.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

125 citing papers in PubMed, 211 citations in OpenAlex.

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  11. Acetyltransferase in cardiovascular disease and aging.The journal of cardiovascular aging · 2024
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65 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Daniel P TeufelMRC Centre for Protein Engineering and Department of Chemistry, Cambridge University, MRC Centre, Hills Road, Cambridge, UK.
Stefan M Freund
Mark Bycroft
Alan R Fersht
Hutchison/MRC Research Centre · GBUniversity of Cambridge · GB

Funding

Medical Research Council MC_U105459896Medical Research Council MC_U105474168
6 · The paper itself

Abstract

The transcriptional coactivator p300 binds to and mediates the transcriptional functions of the tetrameric tumor suppressor p53. Both proteins consist of independently folded domains linked by intrinsically disordered sequences. A well studied short sequence of the p53 transactivation domain, p53(15-29), binds weakly to four folded domains of p300 [Taz1/cysteine-histidine-rich region 1 (CH1), Kix, Taz2/CH3, IBiD], with dissociation constants (K(D)) in the 100 muM region. However, we found that a longer N-terminal transactivation domain construct p53(1-57) bound tightly to each p300 domain. Taz2/CH3 had the greatest affinity (K(D) = 27 nM) and competes with the N-terminal domain of Mdm2 for the p53 N terminus. p300 thus can protect the N terminus of p53 against the binding of other proteins. Mutations of p53 that abrogate transactivation (L22Q/W23S, W53Q/F54S) greatly weakened binding to each p300 domain, linking phenotypic defects to weakened coactivator binding. We propose a complex between tetrameric p53 and p300 in which four domains of p300 wrap around the four transactivation domains of p53.

Indexed as

Transcriptional ActivationAmino Acid SequenceBinding, CompetitiveE1A-Associated p300 ProteinHumansKineticsMagnetic Resonance SpectroscopyModels, BiologicalMolecular Sequence DataMutant ProteinsPeptidesProtein BindingProtein Structure, TertiaryProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53E1A-Associated p300 ProteinEP300 protein, humanMDM2 protein, humanMutant ProteinsPeptidesProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53

Identifiers

PMID17438265
PMCPMC1855428
OpenAlexW2092466076

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.