Dataset: Does inactivation of USP14 enhance degradation of proteasomal substrates that are associated with neurodegenerative diseases? ------------------------------------------------------------------------ **Abstract** A common pathological hallmark of age-related neurodegenerative diseases is the intracellular accumulation of protein aggregates such as α-synuclein in Parkinson’s disease, TDP-43 in ALS, and tau in Alzheimer’s disease. Enhancing intracellular clearance of aggregation-prone proteins is a plausible strategy for slowing progression of neurodegenerative diseases and there is great interest in identifying molecular targets that control protein turnover. One of the main routes for protein degradation is through the proteasome, a multisubunit protease that degrades proteins that have been tagged with a polyubiquitin chain by ubiquitin activating and conjugating enzymes. Published data from cellular models indicate that Ubiquitin-specific protease 14 (USP14), a deubiquitinating enzyme (DUB), slows the degradation of tau and TDP-43 by the proteasome and that an inhibitor of USP14 increases the degradation of these substrates. We conducted similar experiments designed to evaluate tau, TDP-43, or α-synuclein levels in cells after overexpressing USP14 or knocking down endogenous expression by siRNA. Read the [full-text publication][1] by Ortuno, Carlisle, and Miller (*F1000Research*, 2016) for more details. **Data availability** [Figure 1 raw data: Uncropped western blots and intensity values used to generate graphs. Pictures show uncropped membranes probed with antibodies as indicated on the blots. Tables show raw intensity values and ratios to beta-actin intensity values (Arbitrary units). Arb units = arbitrary units.][2] [Figure 2 raw data: Uncropped western blots and intensity values used to generate graphs. Pictures show uncropped membranes probed with antibodies as indicated on the blots. Tables show raw intensity values and ratios to beta-actin intensity values (Arbitrary units). Arb units = arbitrary units. Mock = empty vector control.][3] [Figure 3 raw data: Uncropped western blots and intensity values used to generate graphs. Pictures show uncropped membranes probed with antibodies as indicated on the blots. Tables show raw intensity values and ratios to beta-actin intensity values (Arbitrary units). Arb units = arbitrary units. AS = scrambled control.][4] [Figure 4 raw data: Uncropped western blots and intensity values used to generate graphs. Pictures show uncropped membranes probed with antibodies as indicated on the blots. Tables show raw intensity values and ratios to beta-actin intensity values (Arbitrary units). Arb units = arbitrary units. AS = scrambled control.][5] [Supplemental figure raw data: Uncropped western blots. Pictures show uncropped membranes probed with antibodies as indicated on the blots. Samples from left to right for each blot were empty vector, empty vector, V5-hUSP14wt, V5-hUSP14(CA), empty vector, V5-hUSP14wt, V5-hUSP14(CA), ladder.][6] [1]: http://dx.doi.org/10.12688/f1000research.7800.1 [2]: https://osf.io/34682/ [3]: https://osf.io/tbhgr/ [4]: https://osf.io/3vjtp/ [5]: https://osf.io/wtyd9/ [6]: https://osf.io/ky7zv/