ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
Transcriptional repression of Kruppel like factor-2 by the adaptor protein p66shc.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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.
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.
Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Krüppel-like factor 2 is an endoprotective transcription factor in diabetic kidney disease.American journal of physiology. Cell physiology · 2024Review
- Plxnd1-mediated mechanosensing of blood flow controls the caliber of the Dorsal Aorta via the transcription factor Klf2.bioRxiv : the preprint server for biology · 2024Article
- P66Shc and vascular endothelial function.Bioscience reports · 2019Review
- KLF2 in Regulation of NF-κB-Mediated Immune Cell Function and Inflammation.International journal of molecular sciences · 2017Review
- Insights into the Shc Family of Adaptor Proteins.Journal of molecular signaling · 2017Article
- The role of endothelial mechanosensitive genes in atherosclerosis and omics approaches.Archives of biochemistry and biophysics · 2016Review
- Contrasting expression patterns of coding and noncoding parts of the human genome upon oxidative stress.Scientific reports · 2015Article
- Oxidative stress activates endothelial innate immunity via sterol regulatory element binding protein 2 (SREBP2) transactivation of microRNA-92a.Circulation · 2015Article
- Reduced Krüppel-like factor 2 expression may aggravate the endothelial injury of diabetic nephropathy.Kidney international · 2015Article
- Acute exercise induced mitochondrial H₂O₂ production in mouse skeletal muscle: association with p(66Shc) and FOXO3a signaling and antioxidant enzymes.Oxidative medicine and cellular longevity · 2015Article
- Thrombomodulin and the vascular endothelium: insights into functional, regulatory, and therapeutic aspects.American journal of physiology. Heart and circulatory physiology · 2013Review
- Activated protein C ameliorates diabetic nephropathy by epigenetically inhibiting the redox enzyme p66Shc.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- TNFα signals via p66(Shc) to induce E-Selectin, promote leukocyte transmigration and enhance permeability in human endothelial cells.PloS one · 2013Article
- "Go with the flow": how Krüppel-like factor 2 regulates the vasoprotective effects of shear stress.Antioxidants & redox signaling · 2011Review
- p53 impairs endothelial function by transcriptionally repressing Kruppel-Like Factor 2.Arteriosclerosis, thrombosis, and vascular biology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The adaptor protein p66shc promotes cellular oxidative stress and apoptosis. Here, we demonstrate a novel mechanistic relationship between p66shc and the kruppel like factor-2 (KLF2) transcription factor and show that this relationship has biological relevance to p66shc-regulated cellular oxidant level, as well as KLF2-induced target gene expression. Genetic knockout of p66shc in mouse embryonic fibroblasts (MEFs) stimulates activity of the core KLF2 promoter and increases KLF2 mRNA and protein expression. Similarly, shRNA-induced knockdown of p66shc increases KLF2-promoter activity in HeLa cells. The increase in KLF2-promoter activity in p66shc-knockout MEFs is dependent on a myocyte enhancing factor-2A (MEF2A)-binding sequence in the core KLF2 promoter. Short-hairpin RNA-induced knockdown of p66shc in endothelial cells also stimulates KLF2 mRNA and protein expression, as well as expression of the endothelial KLF2 target gene thrombomodulin. MEF2A protein and mRNA are more abundant in p66shc-knockout MEFs, resulting in greater occupancy of the KLF2 promoter by MEF2A. In endothelial cells, the increase in KLF2 and thrombomodulin protein by shRNA-induced decrease in p66shc expression is partly abrogated by knockdown of MEF2A. Finally, knockdown of KLF2 abolishes the decrease in the cellular reactive oxygen species hydrogen peroxide observed with knockdown of p66shc, and KLF2 overexpression suppresses cellular hydrogen peroxide levels, independent of p66shc expression. These findings illustrate a novel mechanism by which p66shc promotes cellular oxidative stress, through suppression of MEF2A expression and consequent repression of KLF2 transcription.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.