Evidence map›Paper›PMID 29155886›Full record

ArticlePloS one2017

Insights into the mechanism of isoenzyme-specific signal peptide peptidase-mediated translocation of heme oxygenase.

Bianca Schaefer, Kohji Moriishi, Soenke Behrends

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.3field-weighted citation impact, top 39% 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

8 citing papers in PubMed, 12 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Regulation of protein function and degradation by heme, heme responsive motifs, and CO.Critical reviews in biochemistry and molecular biology · 2022
    Review
  5. Review
  6. Article
  7. Article
  8. 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 2 countries.

Bianca SchaeferDepartment of Pharmacology, Toxicology and Clinical Pharmacy, University of Braunschweig-Institute of Technology, Braunschweig, Germany.
Kohji MoriishiDepartment of Microbiology, Faculty of Medicine Yamanashi University, Yamanashi, Japan.
Soenke BehrendsDepartment of Pharmacology, Toxicology and Clinical Pharmacy, University of Braunschweig-Institute of Technology, Braunschweig, Germany.ORCID http://orcid.org/0000-0002-9068-0729
Technische Universität Braunschweig · DEUniversity of Yamanashi · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

It has recently been shown that signal peptide peptidase (SPP) can catalyze the intramembrane cleavage of heme oxygenase-1 (HO-1) that leads to translocation of HO-1 into the cytosol and nucleus. While there is consensus that translocated HO-1 promotes tumor progression and drug resistance, the physiological signals leading to SPP-mediated intramembrane cleavage of HO-1 and the specificity of the process remain unclear. In this study, we used co-immunoprecipitation and confocal laser scanning microscopy to investigate the translocation mechanism of HO-1 and its regulation by SPP. We show that HO-1 and the closely related HO-2 isoenzyme bind to SPP under normoxic conditions. Under hypoxic conditions SPP mediates intramembrane cleavage of HO-1, but not HO-2. In experiments with an inactive HO-1 mutant (H25A) we show that translocation is independent of the catalytic activity of HO-1. Studies with HO-1 / HO-2 chimeras indicate that the membrane anchor, the PEST-domain and the nuclear shuttle sequence of HO-1 are necessary for full cleavage and subsequent translocation under hypoxic conditions. In the presence of co-expressed exogenous SPP, the anchor and the PEST-domain are sufficient for translocation. Taken together, we identified the domains involved in HO-1 translocation and showed that SPP-mediated cleavage is isoform-specific and independent of HO-activity. A closer understanding of the translocation mechanism of HO-1 is of particular importance because nuclear HO-1 seems to lead to tumor progression and drug resistance.

Indexed as

Amino Acid SequenceAspartic Acid EndopeptidasesCell HypoxiaCell MembraneCloning, MolecularGene ExpressionGenetic VectorsHEK293 CellsHeme Oxygenase-1Heme Oxygenase (Decyclizing)HumansMutant Chimeric ProteinsProtein Interaction Domains and MotifsProtein TransportProteolysisSequence AlignmentAspartic Acid EndopeptidasesHeme Oxygenase-1heme oxygenase-2Heme Oxygenase (Decyclizing)HMOX1 protein, humanMutant Chimeric Proteinssignal peptide peptidase

Identifiers

PMID29155886
PMCPMC5695791
OpenAlexW2770350060

What OpenQuestion holds

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LicenceCC BY
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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.