Evidence map›Paper›PMID 26470026›Full record

ArticlePloS one2015

The Effector Domain of MARCKS Is a Nuclear Localization Signal that Regulates Cellular PIP2 Levels and Nuclear PIP2 Localization.

Timothy D Rohrbach, Nishi Shah, William P Jackson, Erin V Feeney, Samantha Scanlon, Robert Gish, Ryan Khodadadi, Stephen O Hyde, Patricia H Hicks, Joshua C Anderson and 2 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

20 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Nuclear Phosphoinositides: Their Regulation and Roles in Nuclear Functions.International journal of molecular sciences · 2019
    Review
  10. Article
  11. Article
  12. Review
  13. MARCKS and Lung Disease.American journal of respiratory cell and molecular biology · 2019
    Review
  14. Article
  15. Review
  16. The Rules and Functions of Nucleocytoplasmic Shuttling Proteins.International journal of molecular sciences · 2018
    Review
  17. Article
  18. Article
  19. 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

12 authors at 1 institution in 1 country.

Timothy D RohrbachThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Nishi ShahThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
William P JacksonThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Erin V FeeneyThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Samantha ScanlonThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Robert GishThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Ryan KhodadadiThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Stephen O HydeThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Patricia H HicksThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Joshua C AndersonThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
John S JarboeThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
Christopher D WilleyThe Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, AL, United States of America.
University of Alabama at Birmingham · US

Funding

XRAY CRYSTALLOGRAPHYP30CA013148 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Robert S Welner · 1985 to 2026
$165.9M
CONTEMPORARY THERAPEUTICS FOR ANAPLASTIC GLIOMASP20CA151129 · NCI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GILLESPIE, G. YANCEY · 2011 to 2013
$2.3M
NCI NIH HHS P20 CA151129NCI NIH HHS P20 CA151129-02NCI NIH HHS P30 CA013148
6 · The paper itself

Abstract

Translocation to the nucleus of diacylglycerol kinase (DGK)- ζ is dependent on a sequence homologous to the effector domain of Myristoylated Alanine Rich C-Kinase Substrate (MARCKS). These data would suggest that MARCKS could also localize to the nucleus. A single report demonstrated immunofluorescence staining of MARCKS in the nucleus; however, further experimental evidence confirming the specific domain responsible for this localization has not been reported. Here, we report that MARCKS is present in the nucleus in GBM cell lines. We then over-expressed wild-type MARCKS (WT) and MARCKS with the effector domain deleted (ΔED), both tagged with V5-epitope in a GBM cell line with low endogenous MARCKS expression (U87). We found that MARCKS-WT localized to the nucleus, while the MARCKS construct without the effector domain remained in the cytoplasm. We also found that over-expression of MARCKS-WT resulted in a significant increase in total cellular phosphatidyl-inositol (4,5) bisphosphate (PIP2) levels, consistent with prior evidence that MARCKS can regulate PIP2 levels. We also found increased staining for PIP2 in the nucleus with MARCKS-WT over-expression compared to MARCKS ΔED by immunofluorescence. Interestingly, we observed MARCKS and PIP2 co-localization in the nucleus. Lastly, we found changes in gene expression when MARCKS was not present in the nucleus (MARCKS ΔED). These data indicate that the MARCKS effector domain can function as a nuclear localization signal and that this sequence is critical for the ability of MARCKS to regulate PIP2 levels, nuclear localization, and gene expression. These data suggests a novel role for MARCKS in regulating nuclear functions such as gene expression.

Indexed as

Active Transport, Cell NucleusAmino Acid SequenceBiological TransportBrain NeoplasmsCell NucleusGene Expression Regulation, NeoplasticGlioblastomaHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsMembrane ProteinsMolecular Sequence DataMyristoylated Alanine-Rich C Kinase SubstrateNuclear Localization SignalsPhosphatidylinositol 4,5-DiphosphateProtein Structure, TertiaryIntracellular Signaling Peptides and ProteinsMARCKS protein, humanMembrane ProteinsMyristoylated Alanine-Rich C Kinase SubstrateNuclear Localization SignalsPhosphatidylinositol 4,5-Diphosphate

Identifiers

PMID26470026
PMCPMC4607481
OpenAlexW2279047888

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.