Evidence map›Paper›PMID 24872192›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2014

Nuclear role of WASp in gene transcription is uncoupled from its ARP2/3-dependent cytoplasmic role in actin polymerization.

Sanjoy Sadhukhan, Koustav Sarkar, Matthew Taylor, Fabio Candotti, Yatin M Vyas

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
3.1field-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

40 citing papers in PubMed, 68 citations in OpenAlex.

  1. Review
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  14. Frontiers in cellular and infection microbiology · 2021
    Article
  15. Wiskott-Aldrich Syndrome Protein: Roles in Signal Transduction in T Cells.Frontiers in cell and developmental biology · 2021
    Review
  16. Review
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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 3 institutions in 1 country.

Sanjoy SadhukhanDivision of Pediatric Hematology-Oncology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15213;
Koustav SarkarDivision of Pediatric Hematology-Oncology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; Division of Pediatric Hematology-Oncology, University of Iowa Children's Hospital, Iowa City, IA 52242; and.
Matthew TaylorDivision of Pediatric Hematology-Oncology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15213;
Fabio CandottiGenetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.
Yatin M VyasDivision of Pediatric Hematology-Oncology, Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center, Pittsburgh, PA 15213; Division of Pediatric Hematology-Oncology, University of Iowa Children's Hospital, Iowa City, IA 52242; and yatin-vyas@uiowa.edu.
University of Pittsburgh Medical Center · USChildren's Hospital of Pittsburgh · USNational Institutes of Health · US

Funding

Molecular and Clinical Studies of Primary ImmunodeficienciesZIAHG000121 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI CANDOTTI, FABIO · 2009 to 2014
$6.2M
Molecular Pathogenesis of Immune Dysfunction In Wiskott-Aldrich-SyndromeR01AI073561 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VYAS, YATIN M · 2008 to 2012
$1.9M
Epigenetic Regulation by WASP of Human TBX21 Gene Transcription ProgramR01AI084957 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VYAS, YATIN M · 2011 to 2014
$1.5M
THE ROLE OF NUCLEAR WASP IN THE TRANSCRIPTIONAL REGULATION OF TH1 DIFFERENTIATIONR21AI079762 · NIAID · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI VYAS, YATIN M · 2008 to 2009
$411k
Intramural NIH HHSNIAID NIH HHS R01 AI073561NIAID NIH HHS R01AI073561NIAID NIH HHS R01 AI084957NIAID NIH HHS R01AI084957NIAID NIH HHS R21 AI079762
6 · The paper itself

Abstract

Defects in Wiskott-Aldrich Syndrome protein (WASp) underlie development of WAS, an X-linked immunodeficiency and autoimmunity disorder of childhood. Nucleation-promoting factors (NPFs) of the WASp family generate F-actin in the cytosol via the VCA (verprolin-homology, cofilin-homology, and acidic) domain and support RNA polymerase II-dependent transcription in the nucleus. Whether nuclear-WASp requires the integration of its actin-related protein (ARP)2/3-dependent cytoplasmic function to reprogram gene transcription, however, remains unresolved. Using the model of human TH cell differentiation, we find that WASp has a functional nuclear localizing and nuclear exit sequences, and accordingly, its effects on transcription are controlled mainly at the level of its nuclear entry and exit via the nuclear pore. Human WASp does not use its VCA-dependent, ARP2/3-driven, cytoplasmic effector mechanisms to support histone H3K4 methyltransferase activity in the nucleus of TH1-skewed cells. Accordingly, an isolated deficiency of nuclear-WASp is sufficient to impair the transcriptional reprogramming of TBX21 and IFNG promoters in TH1-skewed cells, whereas an isolated deficiency of cytosolic-WASp does not impair this process. In contrast, nuclear presence of WASp in TH2-skewed cells is small, and its loss does not impair transcriptional reprogramming of GATA3 and IL4 promoters. Our study unveils an ARP2/3:VCA-independent function of nuclear-WASp in TH1 gene activation that is uncoupled from its cytoplasmic role in actin polymerization.

Indexed as

Actin-Related Protein 2-3 ComplexActinsCell NucleusGATA3 Transcription FactorHeLa CellsHistone-Lysine N-MethyltransferaseHistone MethyltransferasesHumansInterferon-gammaInterleukin-4Jurkat CellsT-bet Transcription FactorT-Box Domain ProteinsTh1 CellsTh2 CellsTranscription, GeneticActin-Related Protein 2-3 ComplexActinsGATA3 protein, humanGATA3 Transcription FactorHistone-Lysine N-MethyltransferaseHistone MethyltransferasesIFNG protein, humanIL4 protein, humanInterferon-gammaInterleukin-4T-bet Transcription FactorT-Box Domain ProteinsWAS protein, humanWiskott-Aldrich Syndrome Protein

Identifiers

PMID24872192
PMCPMC4137324
OpenAlexW1629840740

What OpenQuestion holds

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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.