Evidence map›Paper›PMID 30988205›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Interaction between p53 N terminus and core domain regulates specific and nonspecific DNA binding.

Fan He, Wade Borcherds, Tanjing Song, Xi Wei, Mousumi Das, Lihong Chen, Gary W Daughdrill, Jiandong Chen

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

63 citing papers in PubMed, 98 citations in OpenAlex.

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  7. TowardsbioRxiv : the preprint server for biology · 2025
    Article
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  10. Review
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  12. The multifunctional proline-rich domain of p53 tumor suppressor.Biochimica et biophysica acta. Reviews on cancer · 2025
    Review
  13. Article
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  15. Article
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  20. Review

3 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

8 authors at 3 institutions in 1 country.

Fan HeMolecular Oncology Department, Moffitt Cancer Center, Tampa, FL 33612.
Wade BorcherdsDepartment of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL 33620.
Tanjing SongMolecular Oncology Department, Moffitt Cancer Center, Tampa, FL 33612.
Xi WeiMolecular Oncology Department, Moffitt Cancer Center, Tampa, FL 33612.
Mousumi DasMolecular Oncology Department, Moffitt Cancer Center, Tampa, FL 33612.
Lihong ChenMolecular Oncology Department, Moffitt Cancer Center, Tampa, FL 33612.
Gary W DaughdrillDepartment of Cell Biology, Microbiology, and Molecular Biology, University of South Florida, Tampa, FL 33620; gdaughdrill@usf.edu jiandong.chen@moffitt.org.
Jiandong ChenMolecular Oncology Department, Moffitt Cancer Center, Tampa, FL 33612; gdaughdrill@usf.edu jiandong.chen@moffitt.org.
Molecular Oncology (United States) · USMoffitt Cancer Center · USUniversity of South Florida · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
Mechanisms of p53 activation during stress response (MPI)R01CA141244 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI JIANDONG CHEN, Gary W Daughdrill · 2009 to 2026
$5.3M
Regulation of transcriptional activation by protein disorderR01GM115556 · NIGMS · UNIVERSITY OF SOUTH FLORIDA · PI CHEN, JIANDONG, DAUGHDRILL, GARY W · 2016 to 2023
$2.6M
Function and regulation of MDMX intra-molecular interactionsR01CA186917 · NCI · H. LEE MOFFITT CANCER CTR & RES INST · PI CHEN, JIANDONG · 2015 to 2019
$1.9M
NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA141244NCI NIH HHS R01 CA186917NIGMS NIH HHS R01 GM115556
6 · The paper itself

Abstract

The p53 tumor suppressor is a sequence-specific DNA binding protein that activates gene transcription to regulate cell survival and proliferation. Dynamic control of p53 degradation and DNA binding in response to stress signals are critical for tumor suppression. The p53 N terminus (NT) contains two transactivation domains (TAD1 and TAD2), a proline-rich region (PRR), and multiple phosphorylation sites. Previous work revealed the p53 NT reduced DNA binding in vitro. Here, we show that TAD2 and the PRR inhibit DNA binding by directly interacting with the sequence-specific DNA binding domain (DBD). NMR spectroscopy revealed that TAD2 and the PRR interact with the DBD at or near the DNA binding surface, possibly acting as a nucleic acid mimetic to competitively block DNA binding. In vitro and in vivo DNA binding analyses showed that the NT reduced p53 DNA binding affinity but improved the ability of p53 to distinguish between specific and nonspecific sequences. MDMX inhibits p53 binding to specific target promoters but stimulates binding to nonspecific chromatin sites. The results suggest that the p53 NT regulates the affinity and specificity of DNA binding by the DBD. The p53 NT-interacting proteins and posttranslational modifications may regulate DNA binding, partly by modulating the NT-DBD interaction.

Indexed as

Protein DomainsCell LineDNAEscherichia coliHumansProtein BindingProto-Oncogene Proteins c-mdm2RNA Processing, Post-TranscriptionalTumor Suppressor Protein p53DNAProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53DNA bindingintramolecularNMRp53specificity

Identifiers

PMID30988205
PMCPMC6500136
OpenAlexW2939055665

What Socratic 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 Socratic graph.