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Updated: May 16, 2026
14:08
Study of Protein-protein Interactions in Autophagy Research
Published on: September 9, 2017
Direct interaction between STAT3 and EIF2AK2 controls fatty acid-induced autophagy.
Mireia Niso-Santano1, Shensi Shen, Sandy Adjemian
1INSERM, U848, Villejuif, France.
Autophagy
|December 11, 2012
Summary
STAT3 inhibitors stimulate autophagy by disrupting its interaction with EIF2AK2. This reveals a novel link between fatty acids, inflammation, innate immunity, and translational control in regulating autophagy.
Area of Science:
- Cell Biology
- Molecular Biology
- Immunology
Background:
- Signal transducer and activator of transcription 3 (STAT3) is a pro-inflammatory and oncogenic transcription factor.
- Autophagy, a cellular degradation process, is crucial for maintaining cellular homeostasis.
- STAT3's role in autophagy regulation was previously uncharacterized.
Purpose of the Study:
- To identify novel inducers of autophagy.
- To elucidate the mechanism by which STAT3 regulates autophagy.
- To explore the crosstalk between cellular metabolism, inflammation, innate immunity, and translational control in autophagy.
Main Methods:
- Chemical screening for autophagy inducers.
- Mechanistic studies involving recombinant proteins, pull-down assays, and cell-based experiments.
- Pharmacological and genetic inhibition of STAT3 and EIF2AK2.
- Overexpression of wild-type and mutant STAT3.
- Fatty acid screening for EIF2AK2-dependent autophagy inducers.
Main Results:
- STAT3 inhibitors potently stimulate autophagic flux.
- Cytoplasmic STAT3, not nuclear, regulates autophagy by interacting with EIF2AK2 (PKR).
- STAT3 acts as a competitive inhibitor of EIF2AK2, suppressing autophagy.
- Inhibition of STAT3 or activation of EIF2AK2 (e.g., by fatty acids like palmitate) promotes autophagy.
- Fatty acids trigger autophagy by disrupting the STAT3-EIF2AK2 complex and activating MAPK8/JNK1 and EIF2S1.
Conclusions:
- Autophagy is regulated by cytoplasmic STAT3's interaction with EIF2AK2.
- STAT3 inhibition or EIF2AK2 activation disrupts this complex, inducing autophagy.
- This study uncovers a novel crosstalk between cellular metabolism, inflammation, innate immunity, and translational control in autophagy regulation.
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