Evidence map›Paper›PMID 30003683›Full record

ArticleAging cell2018

CCAR-1 is a negative regulator of the heat-shock response in Caenorhabditis elegans.

Jessica Brunquell, Rachel Raynes, Philip Bowers, Stephanie Morris, Alana Snyder, Doreen Lugano, Andrew Deonarine, Sandy D Westerheide

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging cell, 2018. 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
0.6field-weighted citation impact, top 40% 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. Causality of Aging Hallmarks.Aging and disease · 2025
    Review
  2. Review
  3. Article
  4. The Thermal Stress Coping Network of the NematodeInternational journal of molecular sciences · 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

8 authors at 1 institution in 1 country.

Jessica BrunquellCell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA.
Rachel RaynesCell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA.
Philip BowersCell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA.
Stephanie MorrisCell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA.
Alana SnyderCell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA.
Doreen LuganoCell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA.
Andrew DeonarineCell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA.
Sandy D WesterheideCell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, USA.
University of South Florida · US

Funding

Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
Regulation of the C. elegans heat shock response by LST-3R15AG052149 · NIA · UNIVERSITY OF SOUTH FLORIDA · PI WESTERHEIDE, SANDRA D. · 2016 to 2016
$440k
NIA NIH HHS R15 AG052149NIH HHS P40 OD010440
6 · The paper itself

Abstract

Defects in protein quality control during aging are central to many human diseases, and strategies are needed to better understand mechanisms of controlling the quality of the proteome. The heat-shock response (HSR) is a conserved survival mechanism mediated by the transcription factor HSF1 which functions to maintain proteostasis. In mammalian cells, HSF1 is regulated by a variety of factors including the prolongevity factor SIRT1. SIRT1 promotes the DNA-bound state of HSF1 through deacetylation of the DNA-binding domain of HSF1, thereby enhancing the HSR. SIRT1 is also regulated by various factors, including negative regulation by the cell-cycle and apoptosis regulator CCAR2. CCAR2 negatively regulates the HSR, possibly through its inhibitory interaction with SIRT1. We were interested in studying conservation of the SIRT1/CCAR2 regulatory interaction in Caenorhabditis elegans, and in utilizing this model organism to observe the effects of modulating sirtuin activity on the HSR, longevity, and proteostasis. The HSR is highly conserved in C. elegans and is mediated by the HSF1 homolog, HSF-1. We have uncovered that negative regulation of the HSR by CCAR2 is conserved in C. elegans and is mediated by the CCAR2 ortholog, CCAR-1. This negative regulation requires the SIRT1 homolog SIR-2.1. In addition, knockdown of CCAR-1 via ccar-1 RNAi works through SIR-2.1 to enhance stress resistance, motility, longevity, and proteostasis. This work therefore highlights the benefits of enhancing sirtuin activity to promote the HSR at the level of the whole organism.

Indexed as

Heat-Shock ResponseAcetylationAnimalsCaenorhabditis elegansCaenorhabditis elegans ProteinsDisease Models, AnimalHuntington DiseaseLongevityPeptidesPromoter Regions, GeneticProtein BindingRNA InterferenceRNA, MessengerSirtuinsStress, PhysiologicalTemperatureCaenorhabditis elegans Proteinsheat shock factor-1, C elegansPeptidespolyglutamineRNA, MessengerSIR-2.1 protein, C elegansSirtuinsTranscription FactorsCCAR-1C. elegansheat-shock responseHSF-1longevitySIR-2.1

Identifiers

PMID30003683
PMCPMC6156500
OpenAlexW2884790720

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.