STAT3 as a new autophagy regulator
Barbara Jonchère1, Audrey Bélanger, Catherine Guette
1Paul Papin ICO Cancer Center; Inserm U892; CNRS 6299 and Angers University; Angers, France.
Abstract:
Signal transducers and activators of transcription 3 (STAT3) proteins are cytoplasmic transcription factors that translocate into the nucleus to induce transcription following growth factor or cytokine stimulation. Besides their normal functions, these proteins play an important role in cancer cells through the abnormal activation of cell cycle progression and the deregulation of survival and senescence pathways. New data obtained from the laboratory of Guido Kroemer identifies STAT3 as a new autophagy regulator. In the cytoplasm, in the absence of conventional phosphorylation on the tyrosine 705 residue, STAT3 interacts with the PKR kinase to inhibit eIF2A phosphorylation and so reduce autophagic pathways. This new and nonconventional function of STAT3 has an important role in normal cells but we suggest that it might also affect cancer cells and the response to chemotherapy treatment.
Insights
Signal transducers and activators of transcription 3 (STAT3) proteins regulate autophagy. Unphosphorylated STAT3 inhibits autophagy by interacting with PKR kinase, impacting normal and cancer cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Signal transducers and activators of transcription 3 (STAT3) are transcription factors involved in cell signaling.
- Aberrant STAT3 activation is implicated in cancer progression, affecting cell cycle and survival pathways.
Purpose of the Study:
- To identify novel regulators of autophagy.
- To investigate the role of STAT3 in autophagy.
- To explore the noncanonical functions of STAT3 in cellular processes.
Main Methods:
- Investigated STAT3 protein interactions in the cytoplasm.
- Assessed the impact of STAT3 on eIF2A phosphorylation.
- Studied the effects on autophagic pathways in normal and cancer cells.
Main Results:
- Identified STAT3 as a novel regulator of autophagy.
- Demonstrated that unphosphorylated STAT3 interacts with PKR kinase.
- Showed this interaction inhibits eIF2A phosphorylation, leading to reduced autophagy.
Conclusions:
- STAT3 possesses a nonconventional cytoplasmic function in regulating autophagy.
- This STAT3-mediated autophagy regulation is relevant in normal cells.
- The findings suggest a potential role in cancer cells and chemotherapy response.
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