생화학분자생물학회입니다.
Effects of mTORC1 inhibition on proteasome activity and levels
작성자
Min Jae Lee작성일자
2022-07-19조회수
80Name: Min Jae Lee ( minjlee@snu.ac.kr ) | ||
2015-present | Assistant and Associate Professor, Department of Biochemistry & Molecular Biology, Seoul National University College of Medicine | |
2011-2015 | Assistant Professor, Department of Applied Chemistry, Kyung Hee University | |
2007-2011 | Postdoctoral Fellow, Department of Cell Biology, Harvard Medical School, USA | |
2002-2007 | Ph.D., Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, USA |
Effects of mTORC1 inhibition on proteasome activity and levels
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.
BMB Rep. 2022 Apr;55(4):161-165.
https://pubmed.ncbi.nlm.nih.gov/35321785/