Evidence map›Paper›PMID 24559432›Full record

ArticleJournal of the American Chemical Society2014

The transcriptional complex between the BCL2 i-motif and hnRNP LL is a molecular switch for control of gene expression that can be modulated by small molecules.

Hyun-Jin Kang, Samantha Kendrick, Sidney M Hecht, Laurence H Hurley

Open access · bronzeAbstract read
In one paragraph

Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed
9.4field-weighted citation impact, top 1% 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

119 citing papers in PubMed, 250 citations in OpenAlex.

  1. Polyamines are i-motif disruptors.Molecular therapy. Nucleic acids · 2026
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59 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.

Hyun-Jin KangCollege of Pharmacy and §BIO5 Institute, University of Arizona , Tucson, Arizona 85721, United States.
Samantha Kendrick
Sidney M Hecht
Laurence H Hurley
University of Arizona · US

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Teri L Bankhead · 1985 to 2026
$110.2M
SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
Integrative Cancer Scholars Training GrantT32CA009213 · NCI · UNIVERSITY OF ARIZONA · PI CAREW, JENNIFER S, CURIEL-LEWANDROWSKI, CLARA · 1985 to 2024
$8.6M
G-Quadruplex-Mediated Transcriptional Regulation of PDGFR-??R01CA153821 · NCI · UNIVERSITY OF ARIZONA · PI HURLEY, LAURENCE H., YANG, DANZHOU · 2010 to 2014
$1.9M
Establishing a molecular system for drug targeting of transcriptional controlR01GM085585 · NIGMS · UNIVERSITY OF ARIZONA · PI HURLEY, LAURENCE H. · 2008 to 2011
$1.5M
Targeting DNA Secondary Structures for Bcl-2 Gene RegulationR01GM083117 · NIGMS · UNIVERSITY OF ARIZONA · PI YANG, DANZHOU · 2010 to 2013
$1.2M
NCI NIH HHS CA023074NCI NIH HHS CA153821NCI NIH HHS P30 CA023074NCI NIH HHS R01 CA153821NCI NIH HHS T32 CA009213NCI NIH HHS T32CA09213NIEHS NIH HHS ES06694NIEHS NIH HHS P30 ES006694NIGMS NIH HHS GM083117NIGMS NIH HHS GM085585-01NIGMS NIH HHS GM085585-02S1NIGMS NIH HHS R01 GM083117NIGMS NIH HHS R01 GM085585
6 · The paper itself

Abstract

In a companion paper (DOI: 10.021/ja410934b) we demonstrate that the C-rich strand of the cis-regulatory element in the BCL2 promoter element is highly dynamic in nature and can form either an i-motif or a flexible hairpin. Under physiological conditions these two secondary DNA structures are found in an equilibrium mixture, which can be shifted by the addition of small molecules that trap out either the i-motif (IMC-48) or the flexible hairpin (IMC-76). In cellular experiments we demonstrate that the addition of these molecules has opposite effects on BCL2 gene expression and furthermore that these effects are antagonistic. In this contribution we have identified a transcriptional factor that recognizes and binds to the BCL2 i-motif to activate transcription. The molecular basis for the recognition of the i-motif by hnRNP LL is determined, and we demonstrate that the protein unfolds the i-motif structure to form a stable single-stranded complex. In subsequent experiments we show that IMC-48 and IMC-76 have opposite, antagonistic effects on the formation of the hnRNP LL-i-motif complex as well as on the transcription factor occupancy at the BCL2 promoter. For the first time we propose that the i-motif acts as a molecular switch that controls gene expression and that small molecules that target the dynamic equilibrium of the i-motif and the flexible hairpin can differentially modulate gene expression.

Indexed as

BenzoxazinesCell Line, TumorCholestanesDose-Response Relationship, DrugGene Expression ProfilingHeterogeneous-Nuclear Ribonucleoprotein LHumansMCF-7 CellsPiperidinesPregnanesPromoter Regions, GeneticProto-Oncogene Proteins c-bcl-2Recombinant ProteinsStructure-Activity RelationshipTranscription FactorsBenzoxazinesCholestanesHeterogeneous-Nuclear Ribonucleoprotein LIMC-48IMC-76PiperidinesPregnanesProto-Oncogene Proteins c-bcl-2Recombinant ProteinsTranscription Factors

Identifiers

PMID24559432
PMCPMC3985447
OpenAlexW1972485143

What OpenQuestion holds

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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.