Evidence map›Paper›PMID 20856196›Full record

ArticleOncogene2011

Human AP endonuclease (APE1/Ref-1) and its acetylation regulate YB-1-p300 recruitment and RNA polymerase II loading in the drug-induced activation of multidrug resistance gene MDR1.

S Sengupta, A K Mantha, S Mitra, K K Bhakat

Abstract read
In one paragraph

Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

68 citing papers in PubMed, 118 citations in OpenAlex.

  1. Review
  2. Article
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    Review
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  15. Article
  16. The Relevance of G-Quadruplexes for DNA Repair.International journal of molecular sciences · 2021
    Review
  17. Article
  18. Article
  19. Article
  20. Review

8 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 1 institution in 1 country.

S SenguptaDepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555-1079, USA.
A K Mantha
S Mitra
K K Bhakat
The University of Texas Medical Branch at Galveston · US

Funding

STRUCTURE AND REGULATION OF DNA REPAIR GENES OF MAMMALSR01CA053791 · NCI · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI MITRA, SANKAR · 1991 to 2011
$4.0M
Regulatory Functions of APE1 - An Essential Repair ProteinR01ES008457 · NIEHS · UNIVERSITY OF TEXAS MEDICAL BR GALVESTON · PI MITRA, SANKAR · 1997 to 2010
$3.3M
NCI NIH HHS R01 CA053791NCI NIH HHS R01 CA53791NIEHS NIH HHS P50 ES66076NIEHS NIH HHS R01 ES008457PHS HHS R01ESO8457
6 · The paper itself

Abstract

The overexpression of human apurinic/apyrimidinic (AP) endonuclease 1 (APE1/Ref-1), a key enzyme in the DNA base excision repair (BER) pathway, is often associated with tumor cell resistance to various anticancer drugs. In this study, we examined the molecular basis of transcriptional regulatory (nonrepair) function of APE1 in promoting resistance to certain types of drugs. We have recently shown that APE1 stably interacts with Y-box-binding protein 1 (YB-1), and acts as its coactivator for the expression of multidrug resistance gene MDR1, thereby causing drug resistance. In this study, we show, to the best of our knowledge, for the first time that APE1 is stably associated with the basic transcription factor RNA polymerase II (RNA pol II) and the coactivator p300 on the endogenous MDR1 promoter. The depletion of APE1 significantly reduces YB-1-p300 recruitment to the promoter, resulting in reduced RNA pol II loading. Drug-induced APE1 acetylation, which is mediated by p300, enhances formation of acetylated APE1 (AcAPE1)-YB-1-p300 complex on the MDR1 promoter. Enhanced recruitment of this complex increases MDR1 promoter-dependent luciferase activity and its endogenous expression. Using APE1-downregulated cells and cells overexpressing wild-type APE1 or its nonacetylable mutant, we have demonstrated that the loss of APE1's acetylation impaired MDR1 activation and sensitizes the cells to cisplatin or etoposide. We have thus established the basis for APE1's acetylation-dependent regulatory function in inducing MDR1-mediated drug resistance.

Indexed as

AcetylationATP Binding Cassette Transporter, Subfamily B, Member 1Blotting, WesternDNA-(Apurinic or Apyrimidinic Site) LyaseDNA-Binding ProteinsDrug Resistance, NeoplasmGene Expression RegulationHEK293 CellsHumansImmunoprecipitationNuclear ProteinsOligonucleotide Array Sequence Analysisp300-CBP Transcription FactorsReverse Transcriptase Polymerase Chain ReactionRNA Polymerase IITransfectionAPEX1 protein, humanATP Binding Cassette Transporter, Subfamily B, Member 1DNA-(Apurinic or Apyrimidinic Site) LyaseDNA-Binding ProteinsNuclear Proteinsp300-CBP Transcription FactorsRNA Polymerase IIY-Box-Binding Protein 1YBX1 protein, human

Identifiers

PMID20856196
PMCPMC3010319
OpenAlexW2086061446

What OpenQuestion holds

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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.