p38MAPK: stress responses from molecular mechanisms to therapeutics

By Lydia R. Coulthard, D. E. White, Dominic Jones, M. McDermott, S. Burchill. Trends in Molecular Medicine, 2009

638 citations recorded by the source corpus.

The p38MAPK protein kinases affect a variety of intracellular responses, with well-recognized roles in inflammation, cell-cycle regulation, cell death, development, differentiation, senescence and tumorigenesis. In this review, we examine the regulatory and effector components of this pathway, focusing on their emerging roles in biological processes involved in different pathologies. We summarize how this pathway has been exploited for the development of therapeutics and discuss the potential obstacles of targeting this promiscuous protein kinase pathway for the treatment of different diseases. Furthermore, we discuss how the p38MAPK pathway might be best exploited for the development of more effective therapeutics with minimal side effects in a range of specific disease settings.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d8a3a8fa2f05631bab5bb27869ddffbdc467da80

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In Molecular Biology

1. K. Spriggs
2. R. Seger
3. Anne E. Willis
4. A. Nebreda
5. M. Bushell
6. G. Sabio
7. R. Davis

Citations in the corpus

• The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation. (2011, background): “In addition, p38s were shown to play a role in cardiovascular diseases, and inhibition of this activity has a cardio-protective effect [45].”
• Translational regulation of gene expression during conditions of cell stress. (2010, background): “A major contribution to translational inhibition is mediated by the binding of Hsp27 to eIF4G, which allows its dissociation from the eIF4F complex and PABP into heat shock granules (Cuesta et al., 2000; Ma et al., 2009).”
• Mechanisms and functions of p38 MAPK signalling. (2010, background): “, Cohen, P., Trigon, S., Morange, M., Alonso-Llamazares, A., Zamanillo, D., Hunt, T. and Nebreda, A. R. (1994) A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell 78, 1027–1037 8 Freshney, N. W., Rawlins”