ArticleJCI insight2018
The TAB1-p38α complex aggravates myocardial injury and can be targeted by small molecules.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- P38α deficiency alleviates myocardial ischemia/reperfusion injury by stabilizing c‑Myc to inhibit ferroptosis.Basic research in cardiology · 2026Article
- Karyoptosis mediates cell death and neurodegeneration upon proteotoxic stress.Nature communications · 2026Article
- Targeting of kinases to treat neurodegenerative diseases.Pharmacological reviews · 2026Review
- The stress-activated kinase p38 mediates non-canonical activation of Src and tyrosine phosphorylation of the adapter protein TAB1.The Journal of biological chemistry · 2026Article
- Atypical p38 Kinase Signaling in Retinal Vascular Damage and Recovery.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Role of Atypical MAPK p38 Signaling in the Progression of Influenza A-Induced Acute Lung Injury.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Machine learning identification of key genes in cardioembolic stroke and atherosclerosis: their association with pan-cancer and immune cells.European journal of medical research · 2025Article
- Genetic Encoding of Phosphorylated Amino Acids into Proteins.Chemical reviews · 2024Review
- Characterization of p38α autophosphorylation inhibitors that target the non-canonical activation pathway.Nature communications · 2023Article
- Fluorescence resonance energy transfer (FRET) spatiotemporal mapping of atypical P38 reveals an endosomal and cytosolic spatial bias.Scientific reports · 2023Article
- Diversity and versatility of p38 kinase signalling in health and disease.Nature reviews. Molecular cell biology · 2021Review
- Atypical p38 Signaling, Activation, and Implications for Disease.International journal of molecular sciences · 2021Review
- Subcellular hot spots of GPCR signaling promote vascular inflammation.Current opinion in endocrine and metabolic research · 2021Review
- G protein-coupled receptors activate p38 MAPK via a non-canonical TAB1-TAB2- and TAB1-TAB3-dependent pathway in endothelial cells.The Journal of biological chemistry · 2019Article
- Ubiquitination as a Key Regulator of Endosomal Signaling by GPCRs.Frontiers in cell and developmental biology · 2019Review
- A mouse model for functional dissection of TAB1 O-GlcNAcylation.Wellcome open research · 2019Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Inhibiting MAPK14 (p38α) diminishes cardiac damage in myocardial ischemia. During myocardial ischemia, p38α interacts with TAB1, a scaffold protein, which promotes p38α autoactivation; active p38α (pp38α) then transphosphorylates TAB1. Previously, we solved the X-ray structure of the p38α-TAB1 (residues 384-412) complex. Here, we further characterize the interaction by solving the structure of the pp38α-TAB1 (residues 1-438) complex in the active state. Based on this information, we created a global knock-in (KI) mouse with substitution of 4 residues on TAB1 that we show are required for docking onto p38α. Whereas ablating p38α or TAB1 resulted in early embryonal lethality, the TAB1-KI mice were viable and had no appreciable alteration in their lymphocyte repertoire or myocardial transcriptional profile; nonetheless, following in vivo regional myocardial ischemia, infarction volume was significantly reduced and the transphosphorylation of TAB1 was disabled. Unexpectedly, the activation of myocardial p38α during ischemia was only mildly attenuated in TAB1-KI hearts. We also identified a group of fragments able to disrupt the interaction between p38α and TAB1. We conclude that the interaction between the 2 proteins can be targeted with small molecules. The data reveal that it is possible to selectively inhibit signaling downstream of p38α to attenuate ischemic injury.
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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 Socratic graph.