Physiological State Dictates the Proteasomal-Mediated Purging of Misfolded Protein Fragments

Author(s): Mohamed A. Eldeeb*, Mohamed A. Ragheb, Mansoore Esmaili, Faraz Hussein.

Journal Name: Protein & Peptide Letters

Volume 27 , Issue 3 , 2020

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Abstract:

A pivotal feature that underlies the development of neurodegeneration is the accumulation of protein aggregates. In response, eukaryotic cells have evolved sophisticated quality control mechanisms to identify, repair and/or eliminate the misfolded abnormal proteins. Chaperones identify any otherwise abnormal conformations in proteins and often help them to regain their correct conformation. However, if repair is not an option, the abnormal protein is selectively degraded to prevent its oligomerization into toxic multimeric complexes. Autophagiclysosomal system and the ubiquitin-proteasome system mediate the targeted degradation of the aberrant protein fragments. Despite the increasing understanding of the molecular counteracting responses toward the accumulation of dysfunctional misfolded proteins, the molecular links between the upstream physiological inputs and the clearance of abnormal misfolded proteins is relatively poorly understood. Recent work has demonstrated that certain physiological states such as vigorous exercise and fasting may enhance the ability of mammalian cells to clear misfolded, toxic and aberrant protein fragments. These findings unveil a novel mechanism that activates the cells' protein-disposal machinery, facilitating the adaptation process of cellular proteome to fluctuations in cellular demands and alterations of environmental cues. Herein, we briefly discuss the molecular interconnection between certain physiological cues and proteasomal degradation pathway in the context of these interesting findings and highlight some of the future prospects.

Keywords: Proteasome, protein degradation, aging, neurodegeneration, ubiquitin, protein quality control, N-degron, N-end rule, protein turnover.

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Article Details

VOLUME: 27
ISSUE: 3
Year: 2020
Page: [251 - 255]
Pages: 5
DOI: 10.2174/0929866526666191026111951
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