ArticleCell death and differentiation2016
Proline isomerisation as a novel regulatory mechanism for p38MAPK activation and functions.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
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- Regulation of temozolomide resistance via lncRNAs: Clinical and biological properties of lncRNAs in gliomas (Review).International journal of oncology · 2022Review
- SelectiveAngewandte Chemie (International ed. in English) · 2022Article
- Diversity and versatility of p38 kinase signalling in health and disease.Nature reviews. Molecular cell biology · 2021Review
- Requirement for epithelial p38α in KRAS-driven lung tumor progression.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- A Pan-Cyclophilin Inhibitor, CRV431, Decreases Fibrosis and Tumor Development in Chronic Liver Disease Models.The Journal of pharmacology and experimental therapeutics · 2019Article
- Connexin43 dephosphorylation at serine 282 is associated with connexin43-mediated cardiomyocyte apoptosis.Cell death and differentiation · 2019Article
- The Nuts and Bolts of PIN Auxin Efflux Carriers.Frontiers in plant science · 2019Review
- The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell cycle progression and genomic stability.Nucleic acids research · 2018Article
- Expression of Heat Shock Protein-27 (Hsp27) and P38MAPK in Esophageal Squamous Cell Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- Mapping out p38MAPK.American journal of reproductive immunology (New York, N.Y. : 1989) · 2017Review
- Cancer suppression by systemic inactivation of p38MAPK.Oncotarget · 2017Article
- Xeroderma Pigmentosa Group A (XPA), Nucleotide Excision Repair and Regulation by ATR in Response to Ultraviolet Irradiation.Advances in experimental medicine and biology · 2017Review
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Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stress-induced p38 mitogen-activated protein kinase (MAPK) pathway plays an essential role in multiple physiological processes, including cancer. In turn, p38MAPK phosphorylation at Thr180 and Tyr182 is a key regulatory mechanism for its activation and functions. Here we show that this mechanism is actively regulated through isomerisation of Pro224. Different cyclophilins can isomerise this proline residue and modulate the ability of upstream kinases to phosphorylate Thr180 and Tyr182. In vivo mutation of Pro224 to Ile in endogenous p38MAPK significantly reduced its phosphorylation and activity. This resulted in attenuation of p38MAPK signalling, which in turn caused an enhanced apoptosis and sensitivity to a DNA-damaging drug, cisplatin. We further found a reduction in size and number of lesions in homozygous mice carrying the p38MAPK P224I substitution in a K-ras model of lung tumorigenesis. We propose that cyclophilin-dependent isomerisation of p38MAPK is an important novel mechanism in regulating p38MAPK phosphorylation and functions. Thus, inhibition of this process, including with drugs that are in clinical trials, may improve the efficacy of current anti-cancer therapeutic regimes.
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