Project description:The human adenovirus type 5 (HAdV-C5) early region 1B 55-kDa protein (E1B-55K) is a multifunctional protein that promotes viral replication and adenovirus-mediated cell transformation through various mechanisms that primarily counteract host intrinsic and innate immunity. These include post-translational activities that exploit the host cell ubiquitin- and SUMO-conjugation machineries to regulate antiviral cellular restriction factors. However, despite significant advancements in this field, several underlying mechanisms governing these processes remain unidentified to date. Here, we performed SILAC-based quantitative SUMO proteomics to better understand cellular consequences of E1B-55K-mediated host cell modulation and adenovirus infection in general. We assessed cellular proteins for abundance changes and SUMO2 conjugate proteome changes during infection with wild type HAdV-C5 or E1B-55K deletion mutants. We provide evidence that changes in the SUMOylated proteome have the potential to regulate the DNA damage response, cell cycle control, chromatin assembly, and gene transcription. Strikingly, we identified a SUMO-dependent ubiquitin-mediated degradation mechanism for some SUMO substrates, suggesting that E1B-55K may use multiple mechanisms to alter the activity of restrictive cellular pathways.
