Evidence map›Paper›PMID 31002798›Full record

ArticleCell2019

Protein Sequence Editing of SKN-1A/Nrf1 by Peptide:N-Glycanase Controls Proteasome Gene Expression.

Nicolas J Lehrbach, Peter C Breen, Gary Ruvkun

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
8.4field-weighted citation impact, top 1% 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

80 citing papers in PubMed, 130 citations in OpenAlex.

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  7. NFE2L1/Nrf1 forms a coactivator complex post-peptide:Proceedings of the National Academy of Sciences of the United States of America · 2026
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20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 1 institution in 1 country.

Nicolas J LehrbachDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Peter C BreenDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA.
Gary RuvkunDepartment of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: ruvkun@molbio.mgh.harvard.edu.
Massachusetts General Hospital · US

Funding

GENETIC AND MOLECULAR BASIS OF LONGEVITYR01AG016636 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI GARY B RUVKUN · 1999 to 2026
$12.4M
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
NIA NIH HHS R01 AG016636NIH HHS P40 OD010440
6 · The paper itself

Abstract

The proteasome mediates selective protein degradation and is dynamically regulated in response to proteotoxic challenges. SKN-1A/Nrf1, an endoplasmic reticulum (ER)-associated transcription factor that undergoes N-linked glycosylation, serves as a sensor of proteasome dysfunction and triggers compensatory upregulation of proteasome subunit genes. Here, we show that the PNG-1/NGLY1 peptide:N-glycanase edits the sequence of SKN-1A protein by converting particular N-glycosylated asparagine residues to aspartic acid. Genetically introducing aspartates at these N-glycosylation sites bypasses the requirement for PNG-1/NGLY1, showing that protein sequence editing rather than deglycosylation is key to SKN-1A function. This pathway is required to maintain sufficient proteasome expression and activity, and SKN-1A hyperactivation confers resistance to the proteotoxicity of human amyloid beta peptide. Deglycosylation-dependent protein sequence editing explains how ER-associated and cytosolic isoforms of SKN-1 perform distinct cytoprotective functions corresponding to those of mammalian Nrf1 and Nrf2. Thus, we uncover an unexpected mechanism by which N-linked glycosylation regulates protein function and proteostasis.

Indexed as

Amino Acid SequenceAnimalsAsparagineBortezomibCaenorhabditis elegansCaenorhabditis elegans ProteinsCRISPR-Cas SystemsDNA-Binding ProteinsEndoplasmic ReticulumGene EditingGene Expression RegulationOxidative StressProteasome Endopeptidase ComplexProtein SubunitsSequence AlignmentTranscription FactorsAsparagineBortezomibCaenorhabditis elegans ProteinsDNA-Binding ProteinsProteasome Endopeptidase ComplexProtein Subunitsskn-1 protein, C elegansTranscription Factorsbortezomibdeglycosylationglycobiologyneurodegenerative diseasesNFE2L1NFE2L2NGLY1NGLY1 deficiencyN-linked glycosylationNrf1Nrf2peptide:N-glycanasePNG-1PNGaseproteasomeprotein quality controlprotein sequence editingproteostasisSKN-1SKN-1A

Identifiers

PMID31002798
PMCPMC6574124
OpenAlexW2938145061

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.