Evidence map›Paper›PMID 23303788›Full record

ArticleNucleic acids research2013

Oxygen-dependent expression of cytochrome c oxidase subunit 4-2 gene expression is mediated by transcription factors RBPJ, CXXC5 and CHCHD2.

Siddhesh Aras, Oleg Pak, Natascha Sommer, Russell Finley, Maik Hüttemann, Norbert Weissmann, Lawrence I Grossman

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

101 citing papers in PubMed, 186 citations in OpenAlex.

  1. Article
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  7. CXXC5 is a ubiquitinated protein and is degraded by the ubiquitin-proteasome pathway.Protein science : a publication of the Protein Society · 2025
    Article
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  12. Signal integrator function of CXXC5 in Cancer.Cell communication and signaling : CCS · 2025
    Review
  13. Review
  14. Hif1α-dependent mitochondrial acute ONature communications · 2024
    Article
  15. Article
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  19. Clinical chorioamnionitis at term is characterized by changes in the plasma concentration of CHCHD2/MNRR1, a mitochondrial protein.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2023
    Article
  20. Evidence for the participation of CHCHD2/MNRR1, a mitochondrial protein, in spontaneous labor at term and in preterm labor with intra-amniotic infection.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2023
    Article

41 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

7 authors at 1 institution in 1 country.

Siddhesh ArasCenter for Molecular Medicine and Genetics, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
Oleg Pak
Natascha Sommer
Russell Finley
Maik Hüttemann
Norbert Weissmann
Lawrence I Grossman
Wayne State University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Cytochrome c oxidase (COX) is the terminal enzyme of the electron transport chain, made up of 13 subunits encoded by both mitochondrial and nuclear DNA. Subunit 4 (COX4), a key regulatory subunit, exists as two isoforms, the ubiquitous isoform 1 and the tissue-specific (predominantly lung) isoform 2 (COX4I2). COX4I2 renders lung COX about 2-fold more active compared with liver COX, which lacks COX4I2. We previously identified a highly conserved 13-bp sequence in the proximal promoter of COX4I2 that functions as an oxygen responsive element (ORE), maximally active at a 4% oxygen concentration. Here, we have identified three transcription factors that bind this conserved ORE, namely recombination signal sequence-binding protein Jκ (RBPJ), coiled-coil-helix-coiled-coil-helix domain 2 (CHCHD2) and CXXC finger protein 5 (CXXC5). We demonstrate that RBPJ and CHCHD2 function towards activating the ORE at 4% oxygen, whereas CXXC5 functions as an inhibitor. To validate results derived from cultured cells, we show using RNA interference a similar effect of these transcription factors in the gene regulation of COX4I2 in primary pulmonary arterial smooth muscle cells. Depending on the oxygen tension, a concerted action of the three transcription factors regulates the expression of COX4I2 that, as we discuss, could augment both COX activity and its ability to cope with altered cellular energy requirements.

Indexed as

Gene Expression Regulation, EnzymologicAnimalsBase SequenceCarrier ProteinsCell HypoxiaCells, CulturedDNA-Binding ProteinsElectron Transport Complex IVHEK293 CellsHumansImmunoglobulin J Recombination Signal Sequence-Binding ProteinLungMitochondrial ProteinsMolecular Sequence DataMutationOxygenCarrier ProteinsCHCHD2 protein, humanCOX4I2 protein, humanCXXC5 protein, humanDNA-Binding ProteinsElectron Transport Complex IVImmunoglobulin J Recombination Signal Sequence-Binding ProteinMitochondrial ProteinsOxygenRBPJ protein, humanRepressor ProteinsTrans-ActivatorsTranscription Factors

Identifiers

PMID23303788
PMCPMC3575822
OpenAlexW2024364814

What OpenQuestion holds

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LicenceCC BY-NC
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.