Interactions of the super complexes: When mTORC1 meets the proteasome

Olasunkanmi A.J. Adegoke, Brendan E. Beatty, Scot R. Kimball, Simon S. Wing

Research output: Contribution to journalReview article

Abstract

Homeostatic regulation of energy and metabolic status requires that anabolic and catabolic signaling pathways be precisely regulated and coordinated. Mammalian/mechanistic target of rapamycin complex 1 (mTORC1) is a mega protein complex that promotes energy-consuming anabolic processes of protein and nucleic acid synthesis as well lipogenesis in times of energy and nutrient abundance. However, it is best characterized as the regulator of steps leading to protein synthesis. The ubiquitin-proteasome proteolytic system (UPS) is a major intracellular proteolytic system whose activity is increased during periods of nutrient scarcity and in muscle wasting conditions such as cachexia. Recent studies have examined the impact of mTORC1 on levels and functions of the 26S proteasome, the mega protease complex of the UPS. Here we first briefly review current understanding of the regulation of mTORC1, the UPS, and the 26S proteasome complex. We then review evidence of the effect of each complex on the abundance and functions of the other. Given the fact that drugs that inhibit either complex are either in clinical trials or are approved for treatment of cancer, a muscle wasting condition, we identify studying the effect of combinatory mTORC1-proteasome inhibition on skeletal muscle mass and health as a critical area requiring investigation.

Original languageEnglish (US)
Article number105638
JournalInternational Journal of Biochemistry and Cell Biology
Volume117
DOIs
StatePublished - Dec 2019

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Proteasome Endopeptidase Complex
Ubiquitin
Muscle
Nutrients
Muscle Neoplasms
Food
Lipogenesis
Cachexia
Proteins
Nucleic Acids
Skeletal Muscle
Peptide Hydrolases
Health
Clinical Trials
Muscles
mechanistic target of rapamycin complex 1
Pharmaceutical Preparations
ATP dependent 26S protease

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cell Biology

Cite this

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title = "Interactions of the super complexes: When mTORC1 meets the proteasome",
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Interactions of the super complexes : When mTORC1 meets the proteasome. / Adegoke, Olasunkanmi A.J.; Beatty, Brendan E.; Kimball, Scot R.; Wing, Simon S.

In: International Journal of Biochemistry and Cell Biology, Vol. 117, 105638, 12.2019.

Research output: Contribution to journalReview article

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AU - Kimball, Scot R.

AU - Wing, Simon S.

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