Evidence map›Paper›PMID 20504765›Full record

ArticleThe Journal of biological chemistry2010

S-nitrosylation regulates nuclear translocation of chloride intracellular channel protein CLIC4.

Mariam Malik, Anjali Shukla, Palak Amin, Wendy Niedelman, Jessica Lee, Kasey Jividen, Juanita M Phang, Jinhui Ding, Kwang S Suh, Paul M G Curmi and 1 more

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.8field-weighted citation impact, top 16% 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

26 citing papers in PubMed, 43 citations in OpenAlex.

  1. Science advances · 2026
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  9. Membrane Transporters and Channels in Melanoma.Reviews of physiology, biochemistry and pharmacology · 2021
    Review
  10. Article
  11. Article
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  13. Review
  14. Posttranslational regulation of CYP2J2 by nitric oxide.Free radical biology & medicine · 2018
    Article
  15. Computational Structural Biology ofFrontiers in oncology · 2018
    Review
  16. Article
  17. Article
  18. Article
  19. Chloride intracellular channel 4 is required for maturation of the cerebral collateral circulation.American journal of physiology. Heart and circulatory physiology · 2015
    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

11 authors at 4 institutions in 2 countries.

Mariam MalikLaboratory of Cancer Biology and Genetics, Center for Cancer Research, NCI, National Institutes of Health, Bethesda, MD 20892, USA.
Anjali Shukla
Palak Amin
Wendy Niedelman
Jessica Lee
Kasey Jividen
Juanita M Phang
Jinhui Ding
Kwang S Suh
Paul M G Curmi
Stuart H Yuspa
National Institutes of Health · USCenter for Cancer Research · USSt Vincent's Hospital Sydney · AUUNSW Sydney · AU

Funding

Pathways that Suppress or Accelerate Premalignant Progression of Squamous CancerZIABC005445 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI YUSPA, STUART H. · 2009 to 2022
$15.7M
6 · The paper itself

Abstract

Nuclear translocation of chloride intracellular channel protein CLIC4 is essential for its role in Ca(2+)-induced differentiation, stress-induced apoptosis, and modulating TGF-beta signaling in mouse epidermal keratinocytes. However, post-translational modifications on CLIC4 that govern nuclear translocation and thus these activities remain to be elucidated. The structure of CLIC4 is dependent on the redox environment, in vitro, and translocation may depend on reactive oxygen and nitrogen species in the cell. Here we show that NO directly induces nuclear translocation of CLIC4 that is independent of the NO-cGMP pathway. Indeed, CLIC4 is directly modified by NO through S-nitrosylation of a cysteine residue, as measured by the biotin switch assay. NO enhances association of CLIC4 with the nuclear import proteins importin alpha and Ran. This is likely a result of the conformational change induced by S-nitrosylated CLIC4 that leads to unfolding of the protein, as exhibited by CD spectra analysis and trypsinolysis of the modified protein. Cysteine mutants of CLIC4 exhibit altered nitrosylation, nuclear residence, and stability, compared with the wild type protein likely as a consequence of altered tertiary structure. Moreover, tumor necrosis factor alpha-induced nuclear translocation of CLIC4 is dependent on nitric-oxide synthase activity. Inhibition of nitric-oxide synthase activity inhibits tumor necrosis factor alpha-induced nitrosylation and association with importin alpha and Ran and ablates CLIC4 nuclear translocation. These results suggest that S-nitrosylation governs CLIC4 structure, its association with protein partners, and thus its intracellular distribution.

Indexed as

Active Transport, Cell Nucleusalpha KaryopherinsAnimalsCell DifferentiationChloride ChannelsKeratinocytesMiceMitochondrial ProteinsMutationNIH 3T3 CellsNitric Oxide SynthaseNitrogenOxidation-Reductionran GTP-Binding ProteinTumor Necrosis Factor-alphaalpha KaryopherinsChloride ChannelsCLIC protein, mouseMitochondrial ProteinsNitric Oxide SynthaseNitrogenran GTP-Binding ProteinTumor Necrosis Factor-alpha

Identifiers

PMID20504765
PMCPMC2911286
OpenAlexW2087168695

What OpenQuestion holds

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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.