Post-translational regulation of the mTORC1 pathway: A switch that regulates metabolism-related gene expression

Area of Science:

• Cellular Biology
• Molecular Biology
• Biochemistry

Background:

• The mechanistic target of rapamycin complex 1 (mTORC1) is a central regulator of cell growth, responding to nutrients, growth factors, and energy status.
• mTORC1 activity is critical for anabolic processes; its inhibition promotes catabolism and cellular survival during stress.
• Aberrant mTORC1 signaling is implicated in various diseases, including cancer and metabolic and neurodegenerative disorders.

Purpose of the Study:

• This review elucidates how post-translational modifications (PTMs) regulate the mTORC1 signaling pathway.
• It specifically examines the roles of phosphorylation and ubiquitination in modulating mTORC1 activity.
• The review aims to connect these PTMs to disease pathogenesis and therapeutic strategies.

Main Methods:

• This review synthesizes existing literature on mTORC1 signaling.
• It focuses on studies investigating the impact of phosphorylation and ubiquitination on mTORC1 components.
• The analysis integrates findings related to disease mechanisms and potential drug targets.

Main Results:

• Phosphorylation and ubiquitination are key PTMs that dynamically control mTORC1 complex assembly, localization, and activity.
• Specific phosphorylation sites on mTORC1 components influence its interaction with upstream activators and downstream effectors.
• Ubiquitination can target mTORC1 components for degradation or alter their signaling functions.

Conclusions:

• Post-translational modifications, especially phosphorylation and ubiquitination, are critical regulators of mTORC1 signaling.
• Understanding these modifications provides mechanistic insights into diseases driven by mTORC1 dysregulation.
• Targeting mTORC1-associated PTMs represents a promising therapeutic avenue for cancer and other mTORC1-related pathologies.