Evidence map›Paper›PMID 30723328›Full record

ArticleNature structural & molecular biology2019

Nascent-protein ubiquitination is required for heat shock-induced gene downregulation in human cells.

Fernando Aprile-Garcia, Parul Tomar, Barbara Hummel, Ashkan Khavaran, Ritwick Sawarkar

Abstract read
PubMed Publisher
In one paragraph

Article in Nature structural & molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

28 citing papers in PubMed, 54 citations in OpenAlex.

  1. Principles and mechanisms of plant acclimation to heat stress.Nature reviews. Molecular cell biology · 2026
    Review
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  11. MAPK/MAK/MRK overlapping kinase (MOK) controls microglial inflammatory/type-I IFN responses via Brd4 and is involved in ALS.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Phase separation in gene transcription control.Acta biochimica et biophysica Sinica · 2023
    Review
  13. Review
  14. Transcriptional lockdown during acute proteotoxic stress.Trends in biochemical sciences · 2022
    Review
  15. Article
  16. Article
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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

5 authors at 2 institutions in 1 country.

Fernando Aprile-GarciaMax Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.ORCID http://orcid.org/0000-0002-5133-0857
Parul TomarMax Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Barbara HummelMax Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Ashkan KhavaranMax Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
Ritwick SawarkarMax Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany. sawarkar@ie-freiburg.mpg.de.ORCID http://orcid.org/0000-0003-0532-7662
University of Freiburg · DEMax Planck Institute of Immunobiology and Epigenetics · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Proteotoxic stress such as heat shock causes heat-shock factor (HSF)-dependent transcriptional upregulation of chaperones. Heat shock also leads to a rapid and reversible downregulation of many genes, a process we term stress-induced transcriptional attenuation (SITA). The mechanism underlying this conserved phenomenon is unknown. Here we report that enhanced recruitment of negative transcription elongation factors to gene promoters in human cell lines induces SITA. A chemical inhibitor screen showed that active translation and protein ubiquitination are required for the response. We further find that proteins translated during heat shock are subjected to ubiquitination and that p38 kinase signaling connects cytosolic translation with gene downregulation. Notably, brain samples of subjects with Huntington's disease also show transcriptional attenuation, which is recapitulated in cellular models of protein aggregation similar to heat shock. Thus our work identifies an HSF-independent mechanism that links nascent-protein ubiquitination to transcriptional downregulation during heat shock, with potential ramifications in neurodegenerative diseases.

Indexed as

CytosolDown-RegulationHeat-Shock ProteinsHeat-Shock ResponseHumansHuntington DiseaseMAP Kinase Signaling SystemUbiquitinationHeat-Shock Proteins

Identifiers

PMID30723328
OpenAlexW2914425504

What OpenQuestion holds

Textmetadata
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.