Evidence map›Paper›PMID 23697661›Full record

ArticleBiochemistry2013

Modulation of the CXC chemokine receptor 4 agonist activity of ubiquitin through C-terminal protein modification.

Abhishek Tripathi, Vikas Saini, Adriano Marchese, Brian F Volkman, Wei-Jen Tang, Matthias Majetschak

Open access · greenAbstract read
In one paragraph

Article in Biochemistry, 2013. 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
1.4field-weighted citation impact, top 18% 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, 26 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Cardioprotective Potential of Exogenous Ubiquitin.Cardiovascular drugs and therapy · 2021
    Review
  7. CXCL12 Signaling in the Tumor Microenvironment.Advances in experimental medicine and biology · 2021
    Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Heteromerization of chemokine (C-X-C motif) receptor 4 with α1A/B-adrenergic receptors controls α1-adrenergic receptor function.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  18. Review
  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

6 authors at 2 institutions in 1 country.

Abhishek TripathiDepartment of Surgery, Loyola University Chicago, Stritch School of Medicine, Maywood, Illinois 60153, USA.
Vikas Saini
Adriano Marchese
Brian F Volkman
Wei-Jen Tang
Matthias Majetschak
Medical College of Wisconsin · USUniversity of Chicago · US

Funding

Structural Basis for Chemokine FunctionR01AI058072 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI VOLKMAN, BRIAN F · 2004 to 2019
$4.1M
Structural Basis for Chemokine FunctionR37AI058072 · NIAID · MEDICAL COLLEGE OF WISCONSIN · PI Brian F Volkman · 2020 to 2026
$2.8M
Regulation and Catalysis of Human Insulin Degrading EnzymeR01GM081539 · NIGMS · UNIVERSITY OF CHICAGO · PI TANG, WEI-JEN · 2007 to 2015
$2.6M
Regulation of the Chemokine Receptor CXCR4 by UbiquitinR01GM075159 · NIGMS · LOYOLA UNIVERSITY CHICAGO · PI MARCHESE, ADRIANO · 2007 to 2011
$1.3M
NIAID NIH HHS R01 AI058072NIAID NIH HHS R37 AI058072NIGMS NIH HHS GM075159NIGMS NIH HHS GM081539NIGMS NIH HHS R01 GM075159NIGMS NIH HHS R01 GM081539
6 · The paper itself

Abstract

Extracellular ubiquitin has recently been described as a CXC chemokine receptor (CXCR) 4 agonist. Studies on the structure-function relationship suggested that the C-terminus of ubiquitin facilitates CXCR4 activation. It remains unknown, however, whether C-terminal processing of ubiquitin could be biologically relevant and whether modifications of the ubiquitin C-terminus can modulate CXCR4 activation. We show that C-terminal truncated ubiquitin antagonizes ubiquitin and stromal cell-derived factor (SDF)-1α induced effects on cell signaling and function. Reduction of cell surface expression of insulin degrading enzyme (IDE), which cleaves the C-terminal di-Gly of ubiquitin, enhances ubiquitin induced reduction of cAMP levels in BV2 and THP-1 cells, but does not influence changes in cAMP levels in response to SDF-1α. Reduction of cell surface IDE expression in THP-1 cells also increases the chemotactic activity of ubiquitin. As compared with native ubiquitin, C-terminal Tyr extension of ubiquitin results in reduced CXCR4 mediated effects on cellular cAMP levels and abolishes chemotactic activity. Replacement of C-terminal di-Gly of ubiquitin with di-Val or di-Arg enhances CXCR4 mediated effects on cAMP levels and the di-Arg substitution exerts increased chemotactic activity, when compared with wild type ubiquitin. The chemotactic activities of the di-Val and di-Arg mutants and their effects on cAMP levels can be antagonized with C-terminal truncated ubiquitin. These data suggest that the development of CXCR4 ligands with enhanced agonist activities is possible and that C-terminal processing of ubiquitin could constitute a biological mechanism, which regulates termination of receptor signaling.

Indexed as

AnimalsCell LineCell MembraneCell SeparationChemokine CXCL12Cyclic AMPFlow CytometryGene SilencingHumansInsulinMiceProtein BindingProtein Structure, TertiaryReceptors, CXCR4RNA, Small InterferingSignal TransductionChemokine CXCL12CXCR4 protein, humanCXCR4 protein, mouseCyclic AMPInsulinReceptors, CXCR4RNA, Small InterferingTyrosineUbiquitin

Identifiers

PMID23697661
PMCPMC4113718
OpenAlexW2067573520

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.