Evidence map›Paper›PMID 25778840›Full record

ArticleBiochimie2015

Inhibitor of differentiation 4 (ID4) acts as an inhibitor of ID-1, -2 and -3 and promotes basic helix loop helix (bHLH) E47 DNA binding and transcriptional activity.

Pankaj Sharma, Swathi Chinaranagari, Jaideep Chaudhary

Abstract read
In one paragraph

Article in Biochimie, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

24 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Targeted Disruption of theInternational journal of molecular sciences · 2021
    Article
  7. Article
  8. Alterations in TGFβ signaling during prostate cancer progression.American journal of clinical and experimental urology · 2021
    Review
  9. Article
  10. Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy.International journal of medical sciences · 2020
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. HCRP1, ID4 and Glypican-3: an optimal panel of biomarkers for diagnosis of hepatocellular carcinoma.International journal of clinical and experimental pathology · 2018
    Article
  18. Review
  19. Article
  20. Article
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

3 authors at 2 institutions in 1 country.

Pankaj SharmaCenter for Cancer Research and Therapeutic Development, Clark Atlanta University, 223 James P. Brawley Dr. SW, Atlanta, GA, 30314, USA.
Swathi ChinaranagariCenter for Cancer Research and Therapeutic Development, Clark Atlanta University, 223 James P. Brawley Dr. SW, Atlanta, GA, 30314, USA.
Jaideep ChaudharyCenter for Cancer Research and Therapeutic Development, Clark Atlanta University, 223 James P. Brawley Dr. SW, Atlanta, GA, 30314, USA. Electronic address: jchaudhary@cau.edu.
Atlanta University Center · USCenter for Cancer Research · US

Funding

Technologies/Resources for Core LaboratoriesG12MD007590 · NIMHD · CLARK ATLANTA UNIVERSITY · PI KHAN, SHAFIQ A · 2012 to 2018
$7.6M
Inhibitor of Differentiation Gene Expression and Function in Prostate CellsR01CA128914 · NCI · CLARK ATLANTA UNIVERSITY · PI CHAUDHARY, JAIDEEP · 2009 to 2013
$1.4M
NCI NIH HHS CA128914NCI NIH HHS R01 CA128914NIMHD NIH HHS G12 MD007590NIMHD NIH HHS G12MD007590
6 · The paper itself

Abstract

The four known ID proteins (ID1-4, Inhibitor of Differentiation) share a homologous helix loop helix (HLH) domain and act as dominant negative regulators of basic-HLH transcription factors. ID proteins also interact with many non-bHLH proteins in complex networks. The expression of ID proteins is increasingly observed in many cancers. Whereas ID-1, ID-2 and ID-3, are generally considered as tumor promoters, ID4 on the contrary has emerged as a tumor suppressor. In this study we demonstrate that ID4 heterodimerizes with ID-1, -2 and -3 and promote bHLH DNA binding, essentially acting as an inhibitor of inhibitors of differentiation proteins. Interaction of ID4 was observed with ID1, ID2 and ID3 that was dependent on intact HLH domain of ID4. Interaction with bHLH protein E47 required almost 3 fold higher concentration of ID4 as compared to ID1. Furthermore, inhibition of E47 DNA binding by ID1 was restored by ID4 in an EMSA binding assay. ID4 and ID1 were also colocalized in prostate cancer cell line LNCaP. The alpha helix forming alanine stretch N-terminal, unique to HLH ID4 domain was required for optimum interaction. Ectopic expression of ID4 in DU145 prostate cancer line promoted E47 dependent expression of CDKNI p21. Thus counteracting the biological activities of ID-1, -2 and -3 by forming inactive heterodimers appears to be a novel mechanism of action of ID4. These results could have far reaching consequences in developing strategies to target ID proteins for cancer therapy and understanding biologically relevant ID-interactions.

Indexed as

Basic Helix-Loop-Helix ProteinsInhibitor of Differentiation Protein 1Inhibitor of Differentiation Protein 2Inhibitor of Differentiation ProteinsNeoplasm ProteinsProstatic NeoplasmsTranscription, GeneticCell Line, TumorHumansMaleBasic Helix-Loop-Helix ProteinsID1 protein, humanID2 protein, humanID3 protein, humanID4 protein, humanInhibitor of Differentiation Protein 1Inhibitor of Differentiation Protein 2Inhibitor of Differentiation ProteinsNeoplasm ProteinsTCF3 protein, humanCancerDNA-Protein interactionID4Protein–protein interactionTumor suppressor gene

Identifiers

PMID25778840
PMCPMC4402281
OpenAlexW2010461434

What OpenQuestion holds

Textmetadata
LicenceTDM
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.