Evidence map›Paper›PMID 26268886›Full record

ArticleScientific reports2015

The selective post-translational processing of transcription factor Nrf1 yields distinct isoforms that dictate its ability to differentially regulate gene expression.

Yiguo Zhang, Shaojun Li, Yuancai Xiang, Lu Qiu, Huakan Zhao, John D Hayes

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.2field-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

29 citing papers in PubMed, 62 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Unique and overlapping roles of NRF2 and NRF1 in transcriptional regulation.Journal of clinical biochemistry and nutrition · 2024
    Article
  5. Article
  6. DnaJC7 in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2022
    Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. Overexpression ofInternational journal of molecular sciences · 2020
    Article
  14. Nrf1 Is Endowed with a Dominant Tumor-Repressing Effect onto the Wnt/Oxidative medicine and cellular longevity · 2020
    Article
  15. Glucose Starvation-Induced Rapid Death of Nrf1Oxidative medicine and cellular longevity · 2020
    Article
  16. Article
  17. Article
  18. Article
  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

6 authors at 3 institutions in 2 countries.

Yiguo Zhang1] The NSFC-funded Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China [2] Jacqui Wood Cancer Centre, James Arrott Drive, Division of Cancer Research, Medical Research Institute, Ninewells Hospital &Medical School, University of Dundee, DD1 9SY, Scotland, UK.
Shaojun LiThe NSFC-funded Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
Yuancai XiangThe NSFC-funded Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
Lu QiuThe NSFC-funded Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
Huakan ZhaoThe NSFC-funded Laboratory of Cell Biochemistry and Gene Regulation, College of Medical Bioengineering and Faculty of Life Sciences, Chongqing University, No. 174 Shazheng Street, Shapingba District, Chongqing 400044, China.
John D HayesJacqui Wood Cancer Centre, James Arrott Drive, Division of Cancer Research, Medical Research Institute, Ninewells Hospital &Medical School, University of Dundee, DD1 9SY, Scotland, UK.
Chongqing University · CNNinewells Hospital · GBUniversity of Dundee · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Upon translation, the N-terminal homology box 1 (NHB1) signal anchor sequence of Nrf1 integrates it within the endoplasmic reticulum (ER) whilst its transactivation domains [TADs, including acidic domain 1 (AD1), the flanking Asn/Ser/Thr-rich (NST) domain and AD2] are transiently translocated into the ER lumen, whereupon the NST domain is glycosylated to yield an inactive 120-kDa glycoprotein. Subsequently, these TADs are retrotranslocated into extra-luminal subcellular compartments, where Nrf1 is deglycosylated to yield an active 95-kDa isoform. Herein, we report that AD1 and AD2 are required for the stability of the 120-kDa Nrf1 glycoprotein, but not that of the non-glycosylated/de-glycosylated 95-kDa isoform. Degrons within AD1 do not promote proteolytic degradation of the 120-kDa Nrf1 glycoprotein. However, repositioning of AD2-adjoining degrons (i.e. DSGLS-containing SDS1 and PEST2 sequences) into the cyto/nucleoplasm enables selective topovectorial processing of Nrf1 by the proteasome and/or calpains to generate a cleaved active 85-kDa Nrf1 or a dominant-negative 36-kDa Nrf1γ. Production of Nrf1γ is abolished by removal of SDS1 or PEST2 degrons, whereas production of the cleaved 85-kDa Nrf1 is blocked by deletion of the ER luminal-anchoring NHB2 sequence (aa 81-106). Importantly, Nrf1 activity is positively and/or negatively regulated by distinct doses of proteasome and calpain inhibitors.

Indexed as

Amino Acid SequenceAnimalsCalpainChlorocebus aethiopsCOS CellsEndoplasmic ReticulumGene Expression RegulationHumansNuclear Respiratory Factor 1Proteasome Endopeptidase ComplexProtein IsoformsProtein Processing, Post-TranslationalProteolysisSequence Homology, Amino AcidTranscriptional ActivationCalpainNRF1 protein, humanNuclear Respiratory Factor 1Proteasome Endopeptidase ComplexProtein Isoforms

Identifiers

PMID26268886
PMCPMC4534795
OpenAlexW2404407001

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Registered trials

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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.