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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Effects of mTORC1 inhibition on proteasome activity and levels

  • Park, Seo Hyeong (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine) ;
  • Choi, Won Hoon (BK21 FOUR Biomedical Science Program, Seoul National University College of Medicine) ;
  • Lee, Min Jae (Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine)
  • Received : 2022.02.03
  • Accepted : 2022.03.08
  • Published : 2022.04.30
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Abstract

The mechanistic target of rapamycin (mTOR) regulates numerous extracellular and intracellular signals involved in the maintenance of cellular homeostasis and cell growth. mTOR also functions as an endogenous inhibitor of autophagy. Under nutrient-rich conditions, mTOR complex 1 (mTORC1) phosphorylates the ULK1 complex, preventing its activation and subsequent autophagosome formation, while inhibition of mTORC1 using either rapamycin or nutrient deprivation induces autophagy. Autophagy and proteasomal proteolysis provide amino acids necessary for protein translation. Although the connection between mTORC1 and autophagy is well characterized, the association of mTORC1 inhibition with proteasome biogenesis and activity has not been fully elucidated yet. Proteasomes are long-lived cellular organelles. Their spatiotemporal rather than homeostatic regulation could be another adaptive cellular mechanism to respond to starvation. Here, we reviewed several published reports and the latest research from our group to examine the connection between mTORC1 and proteasome. We have also investigated and described the effect of mTORC1 inhibition on proteasome activity using purified proteasomes. Since mTORC1 inhibitors are currently evaluated as treatments for several human diseases, a better understanding of the link between mTORC1 activity and proteasome function is of utmost importance.

Keywords

Acknowledgement

This work was supported by grants from the NRF (2020R1A5A1019023 and 2021R1A2C2008023 to M.J.L.), the Korea Health Industry Development Institute and Korea Dementia Research Center (HU21C0071 to M.J.L.), and the Creative-Pioneering Researchers Program through Seoul National University, and the BK21 FOUR programs (W.H.C. and S.H.P.).

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