Impaired degradation of PKCα by proteasome in a cellular model of Huntington’s disease

Abstract

In order to investigate any effect of mutant huntingtin aggregation on proteasome function and the degradation of proteins involved in the ubiquitin–proteasome pathway, we studied the degradation of PKCα in Neuro2a cells expressing either normal or mutant truncated huntingtin (HD 16Q and HD 150Q cells). We were able to show an elevation of polyubiquitinated PKCα in HD 150Q cells. PMA treatment of these cells revealed significant delay of PKCα degradation in comparison with control HD 16Q cells. Subcellular fractionation showed association of non-degraded PKCα with the membrane fraction of HD 150Q cells. Our data suggest an impairment of the degradation of PKCα in HD 150Q cells. This impairment is likely to be connected with the sequestration of proteasome on mutant huntingtin aggregates.