Loading...
USP5 enhances SGTA mediated protein quality control.
Hill, J. Nyathi, Yvonne
Hill, J.
Nyathi, Yvonne
Publication Date
2022-07
End of Embargo
Supervisor
Rights
© 2022 Hill, Nyathi. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Peer-Reviewed
Yes
Open Access status
openAccess
Accepted for publication
2022-07-11
Institution
Department
Awarded
Embargo end date
Collections
Additional title
Abstract
Mislocalised membrane proteins (MLPs) present a risk to the cell due to exposed hydrophobic amino acids which cause MLPs to aggregate. Previous studies identified SGTA as a key component of the machinery that regulates the quality control of MLPs. Overexpression of SGTA promotes deubiqutination of MLPs resulting in their accumulation in cytosolic inclusions, suggesting SGTA acts in collaboration with deubiquitinating enzymes (DUBs) to exert these effects. However, the DUBs that play a role in this process have not been identified. In this study we have identified the ubiquitin specific peptidase 5 (USP5) as a DUB important in regulating the quality control of MLPs. We show that USP5 is in complex with SGTA, and this association is increased in the presence of an MLP. Overexpression of SGTA results in an increase in steady-state levels of MLPs suggesting a delay in proteasomal degradation of substrates. However, our results show that this effect is strongly dependent on the presence of USP5. We find that in the absence of USP5, the ability of SGTA to increase the steady state levels of MLPs is compromised. Moreover, knockdown of USP5 results in a reduction in the steady state levels of MLPs, while overexpression of USP5 increases the steady state levels. Our findings suggest that the interaction of SGTA with USP5 enables specific MLPs to escape proteasomal degradation allowing selective modulation of MLP quality control. These findings progress our understanding of aggregate formation, a hallmark in a range of neurodegenerative diseases and type II diabetes, as well as physiological processes of aggregate clearance.
Version
Published version
Citation
Hill J and Nyathi Y (2022) USP5 enhances SGTA mediated protein quality control. PLoS ONE. 17(7): e0257786.
Link to publisher’s version
Link to published version
Link to Version of Record
Type
Article