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.
Eldeeb, M.A.; Fahlman, R.; Ragheb, M.A.; Esmaili, M. Does N-terminal Protein Acetylation lead to protein degradation? BioEssays, 2019. [Epub ahead of print]
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