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Advances in the Study of the Regulatory Roles of mTOR Signaling Pathway Proteins 4E-BP1 and S6K1 in Depression
Received date: 2025-10-13
Revised date: 2025-12-05
Accepted date: 2026-05-26
Online published: 2026-05-26
The mammalian target of rapamycin (mTOR) signaling pathway is a critical conduit for cellular information. Its downstream effectors 4E-BP1 (eIF4E-binding protein 1) and S6K1 (ribosomal protein S6 kinase 1) play pivotal roles in neurogenesis, synaptic remodeling, and antidepressant responses in major depressive disorder. Beginning with the pathological mechanisms of depression and integrating contemporary molecular-biology findings, this review maps the relationship between the mTOR pathway and its effectors 4E-BP1 and S6K1. In the depressive state, mTOR signaling is activated: mTORC1 phosphorylates 4E-BP1, weakening its affinity for eIF4E, thereby releasing eIF4E to facilitate translation initiation and enhance protein synthesis. Concurrently, mTORC1-phosphorylated S6K1 phosphorylates substrates such as ribosomal protein S6 (rpS6), promoting ribosome biogenesis and translational capacity. Elucidating the coordinated actions of 4E-BP1 and S6K1 during depression deepens the molecular understanding of the disease and may inspire novel therapeutic strategies.
LI Jiahua, TIAN Xusheng
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Advances in the Study of the Regulatory Roles of
mTOR Signaling Pathway Proteins 4E-BP1 and S6K1 in Depression
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