p38 Signalling Pathway

Sanz‐Ezquerro, Juan José; Cuenda, Ana

doi:10.3390/ijms22031003

Cited by 20 publications

(10 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…P38MAPK signaling pathway is activated to catalyse the reversible phosphorylation of proteins in response to inflammation ( 148 ). The mechanisms underlying the regulation of SIRT1 by P38MAPK during inflammatory responses remain largely unknown.…”

Section: Sirt1 In the Regulation Of Inflammationmentioning

confidence: 99%

Regulation of SIRT1 and Its Roles in Inflammation

et al. 2022

View full text Add to dashboard Cite

The silent information regulator sirtuin 1 (SIRT1) protein, a highly conserved NAD+-dependent deacetylase belonging to the sirtuin family, is a post-translational regulator that plays a role in modulating inflammation. SIRT1 affects multiple biological processes by deacetylating a variety of proteins including histones and non-histone proteins. Recent studies have revealed intimate links between SIRT1 and inflammation, while alterations to SIRT1 expression and activity have been linked to inflammatory diseases. In this review, we summarize the mechanisms that regulate SIRT1 expression, including upstream activators and suppressors that operate on the transcriptional and post-transcriptional levels. We also summarize factors that influence SIRT1 activity including the NAD+/NADH ratio, SIRT1 binding partners, and post-translational modifications. Furthermore, we underscore the role of SIRT1 in the development of inflammation by commenting on the proteins that are targeted for deacetylation by SIRT1. Finally, we highlight the potential for SIRT1-based therapeutics for inflammatory diseases.

show abstract

Section: Sirt1 In the Regulation Of Inflammationmentioning

confidence: 99%

Regulation of SIRT1 and Its Roles in Inflammation

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Serine/threonine kinase p38 MAP kinase is extensively expressed in endothelial, immune, and inflammatory cells and plays a critical role in the activation of pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) in immune cells. [1] Prostaglandins (PGs), receptor activator of nuclear factor NF-kB ligand (RANKL), and cyclooxygenase-2 (COX-2) are a few of the other inflammatory proteins that arise when TNF-and IL-1 are activated. [2] Inflammatory cytokines or extracellular stressors including heat, mechanical stress, osmotic shock, or UV radiation, activate p38 MAP kinase.…”

Section: Introductionmentioning

confidence: 99%

“…New research indicates that blocking p38 mitogen‐activated protein (MAP) kinase may effectively reduce inflammation. Serine/threonine kinase p38 MAP kinase is extensively expressed in endothelial, immune, and inflammatory cells and plays a critical role in the activation of pro‐inflammatory cytokines such as tumour necrosis factor‐alpha (TNF‐α) and interleukin‐1 beta (IL‐1β) in immune cells [1] . Prostaglandins (PGs), receptor activator of nuclear factor NF‐kB ligand (RANKL), and cyclooxygenase‐2 (COX‐2) are a few of the other inflammatory proteins that arise when TNF‐ and IL‐1 are activated [2] .…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, in vitro Anti‐inflammatory Activity and in silico Studies of Imidazole‐Based 1,2,3‐Triazole Hybrids Targeting p38 MAP Kinase

Awasthi,

Azizur Rahman,

Pingili.

et al. 2024

ChemistrySelect

View full text Add to dashboard Cite

Abstractp38 MAP kinases are involved in numerous inflammatory diseases. A series of 14 molecules of 1,2,3 triazole linked 4‐((2‐cyclohexyl‐4,5‐diphenyl‐1H‐imidazol‐1‐yl) methyl)‐1‐phenyl hybrids(7 a–7 n) has been synthesized by click reaction. Spectral data characterized all the synthesized compounds. The final compounds were screened for in vitro p38 MAP kinase inhibitory activity. Three compounds from the series 7 c, 7 f, and 7 n expounded superior activity with IC50 values 234.08±19.65 nM, 222.68±20.69 nM, and 241.70±20.51 nM respectively while two compounds (7 d and 7 e) showed considerable activity compared to prototype drug Adezmapimod (SB203580) (IC50 value 257.13±23.94 nM). The docking study of synthesized molecules revealed that the three compounds (7 f,7 g, and 7 n) showed higher binding affinities than Adezmapimod. The “Desmond v3.6 Program” was utilized to conduct MD simulations. The result revealed that compound 7 f was conformationally stable. The ADME studies were performed using the Swiss ADME algorithm. Studies revealed that all the compound‘s defiance of Lipinski's rule is within acceptable ranges with few violations. Compound 7 f was orally active and showed good gastrointestinal absorption within the acceptable range. The search for newer compounds with increased activity compared to Adezmapimod resulted in identifying a novel subclass of p38 MAP kinase inhibitors.

show abstract

“…1A ). The direct regulation of ‘upstream’ MAPKKs, alongside autophosphorylation and Arg-methylation based mechanisms of P38 itself, have been proposed to control the signaling outputs of P38 (Johnson and Lapadat, 2002; Sanz-Ezquerro and Cuenda, 2021; Canovas and Nebreda, 2021). The S. pombe P38-related Sty1 MAPK (also known as Spc1) is activated by a wide range of environmental stimuli (Millar et al, 1995; Shiozaki and Russell, 1995; Degols et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

A Peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms

Cao

Day

Galler

et al. 2022

Preprint

View full text Add to dashboard Cite

Peroxiredoxins (Prdx) utilize reversibly oxidized cysteine residues to reduce peroxides but also to promote H2O2 signal transduction, including H2O2-induced activation of P38 MAPK. Prdx form H2O2-induced disulfide complexes with many proteins, including multiple kinases involved in P38 MAPK signaling. Here we show that a genetically-encoded fusion between Prdx and the P38 MAPK is sufficient to hyperactivate the kinase in yeast and human cells by a mechanism that does not require the H2O2-sensing cysteine of the Prdx. In yeast, we demonstrate that a P38-Prdx fusion protein compensates for the loss of a scaffold protein and upstream MAP3K kinase activity, driving entry into mitosis. Based on our findings, we propose that the H2O2-induced formation of Prdx-MAPK disulfide complexes provides a scaffold and signaling platform for MAPKK-MAPK signaling. The demonstration that formation of a complex with a Prdx can be sufficient to modify the activity of a kinase has broad implications for peroxide-based signal transduction in eukaryotes.

show abstract

p38 Signalling Pathway

Abstract: p38 Mitogen activated protein kinases (p38MAPK) are a highly evolutionary conserved group of protein kinases, which are central for cell adaptation to environmental changes as well as for immune response, inflammation, tissue regeneration, and tumour formation [...]

Cited by 20 publications

References 14 publications

Regulation of SIRT1 and Its Roles in Inflammation

Regulation of SIRT1 and Its Roles in Inflammation

Design, Synthesis, in vitro Anti‐inflammatory Activity and in silico Studies of Imidazole‐Based 1,2,3‐Triazole Hybrids Targeting p38 MAP Kinase

A Peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms

Contact Info

Product

Resources

About