PURPOSE: To determine whether the overexpression of the proteasome catalytic beta5 subunit (PSMB5) can induce the expression of the catalytic subunits beta1 and beta2, enhance proteasome activity, and exert a cytoprotective effect in lens epithelial cells. METHODS: Cells from the human lens epithelial cell line SRA01/04 (LECs) were stably transfected either with a plasmid expressing the proteasome catalytic subunit beta5 or with an empty plasmid. beta-5-expressing LECs and controls were analyzed for the expression of beta1, beta2, beta5, and alpha6 proteasome subunits; chymotrypsin-like (CT-L) and peptidylglutamyl-peptide hydrolase (PGPH) catalytic activities; as well as for the accumulation of carbonylated proteins, rates of cell viability, and apoptosis after oxidative stress. RESULTS: Stable expression of the beta5 proteasome subunit resulted in increased expression of the catalytic subunits beta1 and beta2, increased CT-L and PGPH proteasome activities, and increased resistance to accumulation of carbonylated proteins and cell death after oxidative stress. CONCLUSIONS: The proteasome activity can be genetically "upregulated" in lens cells by overexpression of the beta5 catalytic subunit. The resulting increase in proteasome activity leads to a decrease in the accumulation of oxidized proteins and enhanced cell survival following oxidative stress.