Evidence map›Paper›PMID 39513424›Full record

ArticleJournal of cell science2024

Topology surveillance of the lanosterol demethylase CYP51A1 by signal peptide peptidase.

Nikita Sergejevs, Dönem Avci, Michael L van de Weijer, Robin A Corey, Marius K Lemberg, Pedro Carvalho

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cell science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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.

Nikita SergejevsSir William Dunn School of Pathology , University of Oxford, South Parks Road, Oxford OX1 3RE, UK.ORCID 0000-0001-5322-6095
Dönem AvciCenter for Biochemistry and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Michael L van de WeijerSir William Dunn School of Pathology , University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Robin A CoreySchool of Physiology, Pharmacology & Neuroscience, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK.
Marius K LembergCenter for Biochemistry and Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Pedro CarvalhoSir William Dunn School of Pathology , University of Oxford, South Parks Road, Oxford OX1 3RE, UK.ORCID 0000-0002-9691-5277

Funding

University of OxfordWellcome TrustWellcome Trust 223153/Z/21/Z
6 · The paper itself

Abstract

Cleavage of transmembrane segments on target proteins by the aspartyl intramembrane protease signal peptide peptidase (SPP, encoded by HM13) has been linked to immunity, viral infection and protein quality control. How SPP recognizes its various substrates and specifies their fate remains elusive. Here, we identify the lanosterol demethylase CYP51A1 as an SPP substrate and show that SPP-catalysed cleavage triggers CYP51A1 clearance by endoplasmic reticulum-associated degradation (ERAD). We observe that SPP targets only a fraction of CYP51A1 molecules, and we identify an amphipathic helix in the CYP51A1 N terminus as a key determinant for SPP recognition. SPP recognition is remarkably specific to CYP51A1 molecules with the amphipathic helix aberrantly inserted in the membrane with a type II orientation. Thus, our data are consistent with a role for SPP in topology surveillance, triggering the clearance of certain potentially non-functional conformers.

Indexed as

Aspartic Acid EndopeptidasesEndoplasmic ReticulumEndoplasmic Reticulum-Associated DegradationHumansSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSterol 14-DemethylaseSubstrate SpecificityAspartic Acid EndopeptidasesSaccharomyces cerevisiae Proteinssignal peptide peptidaseSterol 14-DemethylaseEndoplasmic reticulumEndoplasmic reticulum-associated protein degradationERADIntramembrane proteolysisProtein quality controlSignal peptide peptidaseSPPUbiquitin ligase

Identifiers

PMID39513424
PMCPMC11827857

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.