Poster Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Uncoupling the mechanisms of protein degradation (#451)

Tom TC Carew 1 , Mary MD Doherty 1 , Phil PW Whitfiled 1
  1. UHI, Inverness, INVERNESS, United Kingdom


Uncoupling the mechanisms of protein degradation

Protein degradation is a fundamental process in the cell which is essential to maintain normal function. Intracellular protein degradation is governed by two major pathways. Proteasomal degradation targets specific proteins and allows sensitive and rapid control of cellular protein composition by the ubiquitin:proteasome (UPS) system. Autophagy involves the mass degradation of proteins in the lysosome. It is believed that these systems are compensatory, however, little is known about how each process contributes to the overall stability of individual proteins. There is a clear need to understand which process is dominant during times of normal cell function and when the cell is subjected to stress. Importantly, disturbances of the protein degradative pathways have been associated with the development a number of prevalent diseases including neurodegenerative disorders. The ability to examine these key pathways at the protein level is therefore critical to the understanding of the molecular basis of disease states. In this study the stability of multiple intracellular proteins have been quantitatively assessed under defined conditions in HEK-293 cells. SILAC-based mass spectrometry methods in conjunction with proteome simplification have been employed to explore the degradative pathways. Gene ontology analysis has revealed novel changes in protein expression when UPS and autophagy are perturbed. These experimental strategies have permitted dissection of the relative control of both pathways and permit further understanding of how protein degradative mechanisms interact and function in cellular systems.


Protein degradation, UPS, Autophagy, SILAC


1Thomas Carew, 2Iain S. Young, Phillip D. Whitfield, Mary K. Doherty

1Division of Biomedical Sciences, University of the Highlands and Islands, Inverness

2School of Medicine, University of Liverpool, Liverpool, UK