The Ubiquitin-Proteasome System (UPS) governs numerous cellular processes by modulating protein stability and activity via the conjugation of the small protein ubiquitin, either as a single molecule or as linkages with distinct functions. Dysregulation of the UPS has been associated with many diseases, including neurodegenerative and neurodevelopmental diseases, as well as cancer. Ubiquitin-conjugating enzymes (E2s) are important players of the UPS that work together with ubiquitin ligases (E3s) to promote substrate ubiquitylation. In this study, we conduct a comparative proteome-wide abundance profiling of S. cerevisiae cells during the exponential growth phase with and without heat shock treatment. We focus on cells with deletions of the two highly homologous E2s, UBC4 or UBC5, and use isobaric tag-based quantitative mass spectrometry to elucidate differences and similarities in their proteomic profiles. Our analysis revealed that the deletion of Ubc4 has a stronger effect on the proteome compared to the deletion of Ubc5, particularly in exponentially growing cells. In contrast, the effect on the proteome of deleting Ubc5 becomes evident only after heat shock, and even then, it remains minor compared to Ubc4. Furthermore, we identified proteins increasing in the absence of each enzyme, which may represent candidate substrates, potentially contributing to a better understanding of their cellular role.

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Journal Article

Authors

Rossio V, Liu X, Paulo JA

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