Abstract
SummaryThe proteasome is essential for the selective degradation of most cellular proteins. To survive overwhelming demands on the proteasome arising during environmental stresses, cells increase proteasome abundance. Proteasome assembly is known to be complex. How stressed cells overcome this vital challenge is unknown. In an unbiased suppressor screen aimed at rescuing the defects of a yeast Rpt6 thermosensitive proteasome mutant, we identified a protein, hereafter named Adc17, as it functions as an ATPase dedicated chaperone. Adc17 interacts with the amino terminus of Rpt6 to assist formation of the Rpt6-Rpt3 ATPase pair, an early step in proteasome assembly. Adc17 is important for cell fitness, and its absence aggravates proteasome defects. The abundance of Adc17 increases upon proteasome stresses, and its function is crucial to maintain homeostatic proteasome levels. Thus, cells have mechanisms to adjust proteasome assembly when demands increase, and Adc17 is a critical effector of this process.
Highlights
Cells normally strive to ensure that proteins get correctly folded and that damaged, mutant, or misfolded proteins are eliminated
The proteasome is essential for the selective degradation of most cellular proteins
In an unbiased suppressor screen aimed at rescuing the defects of a yeast Rpt6 thermosensitive proteasome mutant, we identified a protein, hereafter named Adc17, as it functions as an ATPase dedicated chaperone
Summary
Cells normally strive to ensure that proteins get correctly folded and that damaged, mutant, or misfolded proteins are eliminated. To maintain protein homeostasis under adverse conditions, cells have evolved powerful and sophisticated protein quality control systems that normally operate very efficiently (Kim et al, 2013). Accumulation of misfolded, aggregation-prone proteins is the hallmark of a broad range of human diseases (Cuanalo-Contreras et al, 2013; Kim et al, 2013; Morimoto, 2011; Soto, 2003). When the proteasome is inhibited, cells accumulate undegraded proteins (Kisselev and Goldberg, 2001; Navon and Ciechanover, 2009). Failure of the ubiquitin-proteasome system has been associated with a broad range of pathological conditions, such as the devastating neurodegenerative diseases characterized by the age-dependent deposition of aggregation-prone proteins (Sherman and Goldberg, 2001; Schwartz and Ciechanover, 2009)
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