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Pleiotropic properties of ASK1.
Chihiro Sakauchi1, Hiroaki Wakatsuki1, Hidenori Ichijo1
1The laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Biochimica Et Biophysica Acta. General Subjects
|November 6, 2016
Summary
Apoptosis signal-regulating kinase 1 (ASK1) is vital for cellular homeostasis, particularly under stress. Modulating ASK1 activity offers a promising therapeutic strategy for various diseases by influencing its role beyond apoptosis.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Stress Response
Background:
- Apoptosis signal-regulating kinase 1 (ASK1), or MAP3K5, is implicated in apoptosis induction, especially under oxidative stress.
- Emerging research reveals ASK1's broader, pleiotropic roles in biological systems beyond its apoptotic function.
Purpose of the Study:
- To review the physiological functions of ASK1.
- To elucidate ASK1 regulatory mechanisms and its role in disease pathogenesis.
- To highlight recent advancements in ASK1 research.
Main Methods:
- Review of existing literature and recent publications.
- Analysis of studies involving global and tissue-specific knockout mice.
- Examination of data from ASK1-specific inhibitors.
Main Results:
- ASK1 forms a signalosome complex with regulatory components like thioredoxin (Trx) and TRAFs.
- ASK1's significance in diverse organs and its role in cellular homeostasis under stress are elucidated.
- ASK1 deficiency demonstrates beneficial effects in several disease models.
Conclusions:
- ASK1 is a critical regulator of cellular homeostasis, especially during stress.
- Targeting ASK1 activity presents a promising therapeutic avenue for managing various diseases.
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