In spite of gathering evidence that ubiquitylation can direct non-degradative outcomes, most investigations of ubiquitylation in T cells remain focused on degradation. Here we integrated proteomic and transcriptomic datasets to establish a framework for predicting degradative or non-degradative outcomes of ubiquitylation in primary CD4+ T cells. Di-glycine remnant proteomics revealed ubiquitylated proteins, while whole cell proteomic and transcriptomic data were used to predict whether ubiquitylated proteins showed evidence of degradation. Applying this analysis to ubiquitylated proteins with functions in TCR signaling led us to the prediction that early T cell activation promotes increased non-degradative ubiquitylation. Supporting this, we observed an increase in non-proteasome targeted K29, K33 and K63 polyubiquitin chains during T cell activation, while K48 chains appeared unchanged. This study reveals over 1,200 proteins that are ubiquitylated in primary CD4+ T cells and supports the relevance of non-proteasomally targeted ubiquitin chains in T cell signaling. SOURCE: Joseph,M,Dybas (dybasj@email.chop.edu) -  Children's Hospital of Philadelphia

Pluto Bioinformatics

GSE128154: Integrative proteomics reveals increased non-degradative ubiquitylation during CD4+ T cell activation