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Atypical p38 Signaling, Activation, and Implications for Disease
Jeremy C Burton1, William Antoniades1, Jennifer Okalova1
1Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
International Journal of Molecular Sciences
|April 30, 2021
Summary
The atypical p38 signaling pathway, driven by TAB1 interaction, offers a new therapeutic target for diseases. Disrupting this pathway selectively inhibits pathological p38 activity.
Area of Science:
- Cellular signaling
- Molecular biology
- Pathophysiology
Background:
- Mitogen-activated protein kinase (MAPK) p38 regulates stress and inflammation.
- p38 signaling is implicated in diverse diseases, but therapeutic inhibition remains challenging.
- An atypical p38 pathway, independent of classical routes, is gaining attention.
Purpose of the Study:
- To highlight the pathological significance of the atypical p38 signaling pathway.
- To explore the role of the adaptor protein TAB1 in p38α activation.
- To identify novel therapeutic strategies targeting atypical p38 signaling.
Main Methods:
- Review of recent studies on atypical p38 signaling.
- Analysis of the interaction between TAB1 and p38α.
- Comparison with classical MKK3/6 pathways.
Main Results:
- Atypical p38 signaling involves direct TAB1-p38α interaction, causing autophosphorylation.
- This pathway is selective for p38α and observed in pathophysiological conditions.
- It is linked to inflammation, ischemia, cancer, diabetes, and infections.
Conclusions:
- Atypical p38 signaling is a distinct pathway with significant pathological roles.
- Further research is needed to elucidate its induction mechanisms.
- Selective TAB1-p38 inhibitors present a promising therapeutic avenue.
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