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The Dose-Dependent Pleiotropic Effects of the UBB+1 Ubiquitin Mutant

Katarzyna Banasiak1, Natalia A Szulc1, Wojciech Pokrzywa1

  • 1Laboratory of Protein Metabolism, International Institute of Molecular and Cell Biology in Warsaw, Warsaw, Poland.

Frontiers in Molecular Biosciences
|April 12, 2021
PubMed

Insights

Aging impairs protein degradation, leading to toxic protein buildup. The mutated ubiquitin UBB+1 contributes to neurodegeneration, but low levels may offer protection.

Area of Science:

  • Molecular Biology
  • Neuroscience
  • Aging Research

Background:

  • Proteolytic machinery declines with age, causing aberrant protein accumulation.
  • Cellular proteostasis relies on the ubiquitin-proteasome system (UPS) for protein removal.
  • Aging central nervous system (CNS) cells express mutated ubiquitin (UBB+1), a hallmark of neurodegenerative diseases like Alzheimer's.

Purpose of the Study:

  • To summarize UBB+1's impact on ubiquitin signaling and neurodegeneration.
  • To review how UBB+1 affects UPS components.
  • To explore UBB+1's dose-dependent switch between protective and cytotoxic roles.

Main Methods:

  • Review of recent findings on UBB+1.
  • Analysis of UBB+1's effects on Ub signaling and proteasome function.
  • Examination of UBB+1's role in cell-free and cell-based systems.

Main Results:

  • UBB+1 accumulation is a neuropathological hallmark in tauopathies.
  • Increased UBB+1 disrupts proteasome processivity, promoting toxic protein aggregation.
  • Low UBB+1 levels enhance stress resistance and extend lifespan.

Conclusions:

  • UBB+1 plays a critical, dose-dependent role in neurodegeneration and aging.
  • Understanding UBB+1's dual function is key to developing therapies for age-related proteinopathies.
  • Targeting UBB+1 may offer therapeutic strategies for neurodegenerative diseases.
Keywords:
ROS generation and cytotoxicityUBB+1cellular viabilitymolecular misreadingneurodegenerationproteotoxic stress responseubiquitin proteasomal system

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