Does inactivation of USP14 enhance degradation of proteasomal substrates that are associated with neurodegenerative diseases?

• DOI: 10.12688/f1000research.7800.2
• Publication Date: 2016-04-25T15:05:06Z
• Authors: Daniel Ortuno; Holly J. Carlisle; Silke Miller
• Keywords: Deubiquitinating enzyme; Protein Degradation

<ns4:p>A common pathological hallmark of age-related neurodegenerative diseases is the intracellular accumulation protein aggregates such as α-synuclein in Parkinson’s disease, TDP-43 ALS, and tau Alzheimer’s disease. Enhancing clearance aggregation-prone proteins a plausible strategy for slowing progression there great interest identifying molecular targets that control turnover. One main routes degradation through proteasome, multisubunit protease degrades have been tagged with polyubiquitin chain by ubiquitin activating conjugating enzymes. Published data from cellular models indicate Ubiquitin-specific 14 (USP14), deubiquitinating enzyme (DUB), slows proteasome an inhibitor USP14 increases these substrates. We conducted similar experiments designed to evaluate tau, TDP-43, or levels cells after overexpressing knocking down endogenous expression siRNA.</ns4:p>