Evidence map›Paper›PMID 28011640›Full record

ArticleThe Journal of biological chemistry2017

Regulation of ULK1 Expression and Autophagy by STAT1.

Alexander A Goldberg, Bernard Nkengfac, Anthony M J Sanchez, Nikolay Moroz, Salman T Qureshi, Antonis E Koromilas, Shuo Wang, Yan Burelle, Sabah N Hussain, Arnold S Kristof

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

24 citing papers in PubMed, 42 citations in OpenAlex.

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  20. The Dawn of Mitophagy: What Do We Know by Now?Current neuropharmacology · 2021
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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

10 authors at 4 institutions in 1 country.

Alexander A GoldbergFrom the Departments of Critical Care and Medicine, McGill University Health Centre and Meakins-Christie Laboratories, McGill University, Montreal, Quebec H4A 3J1, Canada.
Bernard NkengfacFrom the Departments of Critical Care and Medicine, McGill University Health Centre and Meakins-Christie Laboratories, McGill University, Montreal, Quebec H4A 3J1, Canada.
Anthony M J SanchezFrom the Departments of Critical Care and Medicine, McGill University Health Centre and Meakins-Christie Laboratories, McGill University, Montreal, Quebec H4A 3J1, Canada.
Nikolay MorozFrom the Departments of Critical Care and Medicine, McGill University Health Centre and Meakins-Christie Laboratories, McGill University, Montreal, Quebec H4A 3J1, Canada.
Salman T QureshiFrom the Departments of Critical Care and Medicine, McGill University Health Centre and Meakins-Christie Laboratories, McGill University, Montreal, Quebec H4A 3J1, Canada.
Antonis E Koromilasthe Lady Davis Institute for Medical Research, McGill University, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
Shuo Wangthe Lady Davis Institute for Medical Research, McGill University, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada.
Yan BurelleFaculty of Pharmacy, Université de Montréal, Montréal, Québec H3T 1J4, Canada.
Sabah N HussainFrom the Departments of Critical Care and Medicine, McGill University Health Centre and Meakins-Christie Laboratories, McGill University, Montreal, Quebec H4A 3J1, Canada.
Arnold S KristofFrom the Departments of Critical Care and Medicine, McGill University Health Centre and Meakins-Christie Laboratories, McGill University, Montreal, Quebec H4A 3J1, Canada. Electronic address: arnold.kristof@mcgill.ca.
McGill University Health Centre · CAJewish General Hospital · CAMcGill University · CAUniversité de Montréal · CA

Funding

mTOR-containing Protein Complexes in the Pathogenesis of Tuberous SclerosisR01CA125436 · NCI · MCGILL UNIVERSITY · PI KRISTOF, ARNOLD · 2007 to 2011
$920k
NCI NIH HHS R01 CA125436
6 · The paper itself

Abstract

Autophagy involves the lysosomal degradation of cytoplasmic contents for regeneration of anabolic substrates during nutritional or inflammatory stress. Its initiation occurs rapidly after inactivation of the protein kinase mammalian target of rapamycin (mTOR) (or mechanistic target of rapamycin), leading to dephosphorylation of Unc-51-like kinase 1 (ULK1) and autophagosome formation. Recent studies indicate that mTOR can, in parallel, regulate the activity of stress transcription factors, including signal transducer and activator of transcription-1 (STAT1). The current study addresses the role of STAT1 as a transcriptional suppressor of autophagy genes and autophagic activity. We show that STAT1-deficient human fibrosarcoma cells exhibited enhanced autophagic flux as well as its induction by pharmacological inhibition of mTOR. Consistent with enhanced autophagy initiation, ULK1 mRNA and protein levels were increased in STAT1-deficient cells. By chromatin immunoprecipitation, STAT1 bound a putative regulatory sequence in the ULK1 5'-flanking region, the mutation of which increased ULK1 promoter activity, and rendered it unresponsive to mTOR inhibition. Consistent with an anti-apoptotic effect of autophagy, rapamycin-induced apoptosis and cytotoxicity were blocked in STAT1-deficient cells but restored in cells simultaneously exposed to the autophagy inhibitor ammonium chloride. In vivo, skeletal muscle ULK1 mRNA and protein levels as well as autophagic flux were significantly enhanced in STAT1-deficient mice. These results demonstrate a novel mechanism by which STAT1 negatively regulates ULK1 expression and autophagy.

Indexed as

AnimalsAutophagyAutophagy-Related Protein-1 HomologCell Line, TumorGene Expression Regulation, EnzymologicHumansIntracellular Signaling Peptides and ProteinsMiceMice, KnockoutPromoter Regions, GeneticSirolimusSTAT1 Transcription FactorAutophagy-Related Protein-1 HomologIntracellular Signaling Peptides and ProteinsSirolimusSTAT1 protein, humanStat1 protein, mouseSTAT1 Transcription FactorULK1 protein, humanUlk1 protein, mouseapoptosisautophagymammalian target of rapamycin (mTOR)proteolysissignal transducers and activators of transcription 1 (STAT1)

Identifiers

PMID28011640
PMCPMC5290961
OpenAlexW2561754441

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.