Impaired degradation of PKCalpha by proteasome in a cellular model of Huntington's disease.
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 PKCalpha 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 PKCalpha in HD 150Q cells. PMA treatment of these cells revealed significant delay of PKCalpha degradation in comparison with control HD 16Q cells. Subcellular fractionation showed association of non-degraded PKCalpha with the membrane fraction of HD 150Q cells. Our data suggest an impairment of the degradation of PKCalpha in HD 150Q cells. This impairment is likely to be connected with the sequestration of proteasome on mutant huntingtin aggregates.
Zemskov
Evgeny A
EA
Laboratory for Structural Neuropathology, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, 351-0198 Saitama, Japan.
Nukina
Nobuyuki
N
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D015536:Down-Regulation / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D051379:Mice; D009097:Multienzyme Complexes / Q000494:pharmacology*; D009154:Mutation / Q000235:genetics; D009447:Neuroblastoma / Q000201:enzymology; D011233:Precipitin Tests; D046988:Proteasome Endopeptidase Complex; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D025801:Ubiquitin / Q000378:metabolism
D009097:Multienzyme Complexes; D025801:Ubiquitin; C496628:PRKCA protein, human; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D013755:Tetradecanoylphorbol Acetate