Evidence map›Paper›PMID 25653282›Full record

ArticleThe Journal of biological chemistry2015

Proteasomal modulation of cellular SNAT2 (SLC38A2) abundance and function by unsaturated fatty acid availability.

Francesca Nardi, Thorsten M Hoffmann, Clare Stretton, Emma Cwiklinski, Peter M Taylor, Harinder S Hundal

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.2field-weighted citation impact, top 9% 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

22 citing papers in PubMed, 43 citations in OpenAlex.

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  13. Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Article
  14. Article
  15. Article
  16. Review
  17. Lipid modulation of skeletal muscle mass and function.Journal of cachexia, sarcopenia and muscle · 2017
    Review
  18. Article
  19. Characterization of 5-(2-F1000Research · 2016
    Article
  20. 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 at 1 institution in 1 country.

Francesca NardiFrom the Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom.
Thorsten M HoffmannFrom the Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom.
Clare StrettonFrom the Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom.
Emma CwiklinskiFrom the Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom.
Peter M TaylorFrom the Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom.
Harinder S HundalFrom the Division of Cell Signalling and Immunology, Sir James Black Centre, College of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom h.s.hundal@dundee.ac.uk.
University of Dundee · GB

Funding

Biotechnology and Biological Sciences Research CouncilWellcome Trust
6 · The paper itself

Abstract

Expression and activity of the System A/SNAT2 (SLC38A2) amino acid transporter is up-regulated by amino acid starvation and hypertonicity by a mechanism dependent on both ATF4-mediated transcription of the SLC38A2 gene and enhanced stabilization of SNAT2 itself, which forms part of an integrated cellular stress response to nutrient deprivation and osmotic stress. Here we demonstrate that this adaptive increase in System A function is restrained in cells subjected to prior incubation with linoleic acid (LOA, an unsaturated C18:2 fatty acid) for 24 h. While fatty acid treatment had no detectable effect upon stress-induced SNAT2 or ATF4 gene transcription, the associated increase in SNAT2 protein/membrane transport activity were strongly suppressed in L6 myotubes or HeLa cells preincubated with LOA. Cellular ubiquitination of many proteins was increased by LOA and although the fatty acid-induced loss of SNAT2 could be attenuated by proteasomal inhibition, the functional increase in System A transport activity associated with amino acid starvation/hypertonicity that depends upon processing/maturation and delivery of SNAT2 to the cell surface could not be rescued. LOA up-regulated cellular expression of Nedd4.2, an E3-ligase implicated in SNAT2 ubiquitination, but shRNA-directed Nedd4.2 gene silencing could not curb fatty acid-induced loss of SNAT2 adaptation. However, expression of SNAT2 in which seven putative lysyl-ubiquitination sites in the cytoplasmic N-terminal domain were mutated to alanine protected SNAT2 against LOA-induced proteasomal degradation. Collectively, our findings indicate that increased availability of unsaturated fatty acids can compromise the stress-induced induction/adaptation in SNAT2 expression and function by promoting its degradation via the ubiquitin-proteasome system.

Indexed as

Amino Acid Transport System AAnimalsEndosomal Sorting Complexes Required for TransportHEK293 CellsHeLa CellsHumansLinoleic AcidMuscle Fibers, SkeletalNedd4 Ubiquitin Protein LigasesOsmotic PressureProteasome Endopeptidase ComplexRatsTranscription, GeneticUbiquitin-Protein LigasesUp-RegulationAmino Acid Transport System AEndosomal Sorting Complexes Required for TransportLinoleic AcidNedd4L protein, humanNEDD4L protein, ratNedd4 protein, humanNedd4 protein, ratNedd4 Ubiquitin Protein LigasesProteasome Endopeptidase ComplexSLC38A2 protein, humanUbiquitin-Protein Ligasesamino acid transportAmino acid transporterATF4fatty acidhypertonicityLinoleic acidmuscleproteasomeSNAT2ubiquitin

Identifiers

PMID25653282
PMCPMC4375474
OpenAlexW2047933315

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.