Evidence map›Paper›PMID 26602861›Full record

ArticleTraffic (Copenhagen, Denmark)2016

RNF121 Inhibits Angiogenic Growth Factor Signaling by Restricting Cell Surface Expression of VEGFR-2.

Armin Maghsoudlou, Rosana D Meyer, Kobra Rezazadeh, Emad Arafa, Jeffrey Pudney, Edward Hartsough, Nader Rahimi

Open access · bronzeAbstract read
In one paragraph

Article in Traffic (Copenhagen, Denmark), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.9field-weighted citation impact, top 25% 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

12 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. KIF13B mediates VEGFR2 recycling to modulate vascular permeability.Cellular and molecular life sciences : CMLS · 2023
    Article
  4. Ubiquitin-mediated degradation at the Golgi apparatus.Frontiers in molecular biosciences · 2023
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. 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

7 authors at 2 institutions in 1 country.

Armin MaghsoudlouDepartment of Pathology and Laboratory Medicine, Boston University Medical Campus, Boston, MA 02118, USA.
Rosana D MeyerDepartment of Pathology and Laboratory Medicine, Boston University Medical Campus, Boston, MA 02118, USA.
Kobra RezazadehDepartment of Pathology and Laboratory Medicine, Boston University Medical Campus, Boston, MA 02118, USA.
Emad ArafaDepartment of Pathology and Laboratory Medicine, Boston University Medical Campus, Boston, MA 02118, USA.
Jeffrey PudneyDepartment of Obstetrics & Gynecology, Boston University Medical Campus, Boston, MA 02118, USA.
Edward HartsoughDepartment of Pathology and Laboratory Medicine, Boston University Medical Campus, Boston, MA 02118, USA.
Nader RahimiDepartment of Pathology and Laboratory Medicine, Boston University Medical Campus, Boston, MA 02118, USA.
Boston Medical Center · USBoston University · US

Funding

VEGFR-1 and VEGFR-2 in angiogenesisR01EY012997 · NEI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAHIMI, NADER · 2002 to 2006
$1.6M
Role of Protein Ubiquitination in AngiogenesisR01EY017955 · NEI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAHIMI, NADER · 2008 to 2010
$1.2M
Overcoming the resistance to anti-angiogenesis therapyR21CA191970 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAHIMI, NADER · 2015 to 2016
$392k
IGPR-1 in colon cancer chemotherapyR21CA193958 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAHIMI, NADER · 2015 to 2016
$392k
NCI NIH HHS R21 CA191970NCI NIH HHS R21CA191970NCI NIH HHS R21 CA193958NCI NIH HHS R21CA193958NEI NIH HHS R01 EY012997NEI NIH HHS R01 EY017955
6 · The paper itself

Abstract

Ligand stimulation promotes downregulation of RTKs, a mechanism by which RTKs, through the ubiquitination pathway are removed from the cell surface, causing a temporary termination of RTK signaling. The molecular mechanisms governing RTK trafficking and maturation in the endoplasmic reticulum (ER)/Golgi compartments are poorly understood. Vascular endothelial growth factor receptor-2 (VEGFR-2) is a prototypic RTK that plays a critical role in physiologic and pathologic angiogenesis. Here we demonstrate that Ring Finger Protein 121 (RNF121), an ER ubiquitin E3 ligase, is expressed in endothelial cells and regulates maturation of VEGFR-2. RNF121 recognizes newly synthesized VEGFR-2 in the ER and controls its trafficking and maturation. Over-expression of RNF121 promoted ubiquitination of VEGFR-2, inhibited its maturation and resulted a significantly reduced VEGFR-2 presence at the cell surface. Conversely, the shRNA-mediated knockdown of RNF121 in primary endothelial cells reduced VEGFR-2 ubiquitination and increased its cell surface level. The RING Finger domain of RNF121 is required for its activity toward VEGFR-2, as its deletion significantly reduced the effect of RNF121 on VEGFR-2. Additionally, RNF121 inhibited VEGF-induced endothelial cell proliferation and angiogenesis. Taken together, these data identify RNF121 as a key determinant of angiogenic signaling that restricts VEGFR-2 cell surface presence and its angiogenic signaling.

Indexed as

Signal TransductionAnimalsCell MembraneCell ProliferationEndoplasmic ReticulumHEK293 CellsHT29 CellsHumansHuman Umbilical Vein Endothelial CellsMembrane ProteinsProtein TransportSwineUbiquitinationVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2Membrane Proteinsring finger protein 121, humanVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2angiogenesisendoplasmic reticulum ubiquitin E3 ligasereceptor tyrosine kinaseRING Finger protein 121ubiquitinationVEGFR-2

Identifiers

PMID26602861
PMCPMC4767591
OpenAlexW2175236421

What OpenQuestion holds

Textmetadata
LicenceTDM
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.