Expression profiling of the ubiquitin conjugating enzyme UbcM2 in murine brain reveals modest age-dependent decreases in specific neurons.

UbcM2 is a ubiquitin-conjugating enzyme with roles in the turnover of damaged and misfolded proteins, cell cycle progression, development, and regulation of the antioxidant transcription factor, Nrf2. Recent screens have identified binding partners of the enzyme that are associated with various neurodegenerative diseases, and our previous studies have shown that UbcM2 is enriched in retina and brain. In the current study, we characterized UbcM2 protein expression in various structures and cell types in the murine brain. Immunofluorescence analysis of paraffin-embedded brain sections revealed that UbcM2 is ubiquitously expressed throughout the brain, is enriched in hindbrain and cortex, and is robustly expressed in neurons. In contrast, the enzyme is undetectable in most astrocytes and microglia. As dysfunction of the ubiquitin proteasome system (UPS) has been linked to many age-related neurological diseases, we compared UbcM2 expression levels in young versus aged wild-type mice and found a global decrease in expression in aged brains, with reductions of 10 % or greater in five substructures (cerebellar granule cell layer, primary motor cortex, olfactory nucleus, superior colliculus, and secondary visual cortex). These studies represent the first protein expression profiling of a ubiquitin-conjugating enzyme in the brain and support the notion that deficits in protein degradation and proteostasis associated with neurodegenerative diseases may be, in part, attributable to age-dependent reductions in the enzymatic machinery of the UPS.