Evidence map›Paper›PMID 12853978›Full record

ArticleOncogene2003

Downregulation of epidermal growth factor receptor signaling by singlet oxygen through activation of caspase-3 and protein phosphatases.

Shougang Zhuang, Gladys D Ouedraogo, Irene E Kochevar

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

21 citing papers in PubMed, 54 citations in OpenAlex.

  1. Article
  2. Article
  3. WNK1 controls endosomal trafficking through TRIM27-dependent regulation of actin assembly.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
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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

3 authors at 2 institutions in 1 country.

Shougang ZhuangWellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Gladys D Ouedraogo
Irene E Kochevar
Massachusetts General Hospital · USHarvard University · US

Funding

ULTRAVIOLET LIGHT-INDUCED PHENOMENA IN BIOMEMBRANESR01GM030755 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI KOCHEVAR, IRENE · 1985 to 2006
$1.4M
NIGMS NIH HHS GM 30755
6 · The paper itself

Abstract

Downregulation of survival signaling pathways contributes to the cytotoxicity of reactive oxygen species (ROS) and may underlie certain therapies for hyperproliferative diseases. We have investigated the role of singlet oxygen, an ROS formed by photosensitization, in the regulation of survival signaling via the epidermal growth factor receptor (EGFR). Exposure of human keratinocytes to singlet oxygen resulted in rapid loss of EGFR, which was not blocked by either inhibition of receptor internalization or by interrupting the major proteolytic pathways (proteasome, lysosome or calpain). However, pretreatment with a caspase-3 inhibitor, DEVD-FMK, inhibited EGFR degradation. Caspase-3 cleavage was detected as early as 5 min after singlet oxygen treatment, and recombinant active caspase-3 completely cleaved EGFR in a keratinocyte membrane fraction. The singlet oxygen-induced loss of EGFR was accompanied by dephosphorylation of EGFR as well as of Akt and extracellular signal-regulated kinase 1/2 (ERK)1/2. Singlet oxygen-induced protein dephosphorylation was not dependent on activation of caspase-3. In contrast, inhibition of protein phosphatases (PPs) with okadaic acid completely blocked dephosphorylation of EGFR, ERK1/2 and Akt as well as degradation of EGFR. These results indicate that the oxidative stress produced by singlet oxygen rapidly disrupts EGFR-mediated signaling by decreasing both the protein level and its phosphorylation. These responses depended on intertwined activation of caspase-3 and PPs.

Indexed as

Protein Serine-Threonine KinasesApoptosisCaspase 3CaspasesCells, CulturedCysteine EndopeptidasesDimerizationDown-RegulationEndocytosisEnzyme ActivationErbB ReceptorsHumansKeratinocytesMitogen-Activated Protein KinasesMultienzyme ComplexesPhosphoprotein PhosphatasesAKT1 protein, humanCASP3 protein, humanCaspase 3CaspasesCysteine EndopeptidasesErbB ReceptorsMitogen-Activated Protein KinasesMultienzyme ComplexesPhosphoprotein PhosphatasesProteasome Endopeptidase ComplexProtein Serine-Threonine KinasesProto-Oncogene ProteinsProto-Oncogene Proteins c-aktReceptors, Platelet-Derived Growth FactorSinglet Oxygen

Identifiers

PMID12853978
OpenAlexW1972692044

What OpenQuestion holds

Textmetadata
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.