The Dose-Dependent Pleiotropic Effects of the UBB Ubiquitin Mutant

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2021 Apr 12

PMID 33842548

Citations 2

Authors

Katarzyna Banasiak

Natalia A Szulc

Wojciech Pokrzywa

Affiliations

Soon will be listed here.

Abstract

The proteolytic machinery activity diminishes with age, leading to abnormal accumulation of aberrant proteins; furthermore, a decline in protein degradation capacity is associated with multiple age-related proteinopathies. Cellular proteostasis can be maintained the removal of ubiquitin (Ub)-tagged damaged and redundant proteins by the ubiquitin-proteasome system (UPS). However, during aging, central nervous system (CNS) cells begin to express a frameshift-mutated Ub, UBB. Its accumulation is a neuropathological hallmark of tauopathy, including Alzheimer's disease and polyglutamine diseases. Mechanistically, in cell-free and cell-based systems, an increase in the UBB concentration disrupts proteasome processivity, leading to increased aggregation of toxic proteins. On the other hand, a low level of UBB improves stress resistance and extends lifespan. Here we summarize recent findings regarding the impact of UBB on Ub signaling and neurodegeneration. We also review the molecular basis of how UBB affects UPS components as well as its dose-dependent switch between cytoprotective and cytotoxic roles.

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