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The cGAS-STING/PERK-eIF2α: Individual or Potentially Collaborative Signaling Transduction in Cardiovascular Diseases
Xueqi Wan1, Huan Zhang1, Jinfan Tian1
1Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Disease, Beijing 100029, P.R. China.
International Journal of Biological Sciences
|December 12, 2024
Summary
The cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway noncanonically activates the protein kinase RNA-like ER kinase (PERK)-eukaryotic initiation factor 2α (eIF2α) pathway. This crosstalk may contribute to cardiovascular diseases (CVDs).
Area of Science:
- Immunology
- Cellular Biology
- Cardiovascular Research
Background:
- The cyclic GMP-AMP (cGAMP) synthase (cGAS)-stimulator of interferon genes (STING) pathway is a canonical mediator of type I interferon (IFN) release.
- This pathway typically involves TANK-binding kinase 1 (TBK1) and IFN regulatory factor 3 (IRF3).
Purpose of the Study:
- To investigate the noncanonical activation of the protein kinase RNA-like ER kinase (PERK)-eukaryotic initiation factor 2α (eIF2α) pathway by cGAS-STING.
- To explore the bidirectional crosstalk between the cGAS-STING and PERK-eIF2α pathways.
- To elucidate the role of this signaling axis in the pathophysiology of cardiovascular diseases (CVDs).
Main Methods:
- Investigated the noncanonical activation of PERK-eIF2α by cGAS-STING.
- Analyzed the regulatory role of PERK on STING signaling.
- Examined the functional crosstalk between these pathways.
Main Results:
- The cGAS-STING pathway noncanonically activates the PERK-eIF2α pathway, an unfolded protein response (UPR) branch.
- PERK was found to regulate STING signaling, indicating a bidirectional crosstalk.
- Convergent downstream signaling from both pathways may contribute to CVDs.
Conclusions:
- A novel cGAS-STING/PERK-eIF2α signaling axis is identified.
- This axis represents a new pathway contributing to the development of cardiovascular diseases.
- This finding provides a foundation for potential therapeutic targets for CVDs.
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