Global profiling of lysine ubiquitylation in human hypothalamus

Abstract

Ubiquitylation, a critical post-translational modification, regulates various biological pathways. Despite its implications in diseases like cancer, the ubiquitinome of the human hypothalamus remains inadequately explored. We conducted label-free ubiquitinome analysis on hypothalamus samples from healthy elderly individuals, identifying 21,815 ubiquitylated sites across 5,314 proteins. Motif analysis revealed specific residue preferences. Functional enrichment analysis revealed significant roles in cellular processes, particularly in transport and catabolism pathways. Analysis of E3 ligase and deubiquitinating enzyme substrates emphasized dynamic protein turnover regulation. Integration with pathway analysis unveiled the significance of ubiquitinated proteins in neurological pathways, underscoring their relevance to neurological function and dysfunction. This study provides crucial insights into hypothalamic ubiquitination, highlighting the pressing need for further investigation into ubiquitin-mediated pathways in neurological disorders.