Meta-analysis fails to show any correlation between protein abundance and ubiquitination changes

Ubiquitination serves as a key regulatory mechanism in nearly all cellular processes, though it was originally identified as a post-translational modification that targets proteins for degradation. Accordingly, these two molecular events have since been tightly linked, and changes in protein abundance are frequently interpreted as indirect indicators of ubiquitination dynamics. Nevertheless, the relationship between protein abundance and ubiquitination has not been systematically examined across distinct biological systems. Here, we conducted a comprehensive meta-analysis to assess the correlation between protein abundance and ubiquitination levels determined by mass spectrometry in mammals, plants, and yeast. Quantitative proteomics and diGly-ubiquitin peptides data from 19 independent studies encompassing over 50 experimental conditions were analyzed. The findings indicate that alterations in protein abundance cannot reliably be used to infer ubiquitination events - and vice versa - highlighting the need for caution when interpreting proteomic data as a proxy for ubiquitin-mediated regulation.