Post-translational modifications (PTMs) allow cells to rapid…

Pоst-trаnslаtiоnаl mоdifications (PTMs) allow cells to rapidly regulate protein function, localization, and interactions. While ubiquitination is best known for targeting proteins for proteasomal degradation, SUMOylation (Small Ubiquitin-like Modifier conjugation) represents a distinct pathway. SUMO proteins are covalently attached to lysine residues via an enzymatic cascade involving E1-activating, E2-conjugating, and E3-ligating enzymes. Unlike ubiquitination, SUMOylation does not typically signal degradation. Instead, it modifies protein-protein interactions, subcellular localization, and chromatin states. Histones are important SUMOylation substrates. For example, SUMOylation of histone H4 is associated with recruitment of histone deacetylases (HDACs), leading to local transcriptional repression. Conversely, ubiquitination of histone H2B (H2Bub1) is linked to transcriptional elongation and crosstalk with activating methylation marks (H3K4me3, H3K79me). SUMOylation is reversible, mediated by SUMO-specific proteases (SENPs), allowing dynamic regulation of nuclear events. Dysregulation of SUMOylation has been implicated in cancer progression and neurodegenerative diseases. Based on the passage, which of the following experimental outcomes would most strongly support the functional distinction between SUMOylation and ubiquitination?