title: Ubiquitin-binding protein p62 expression is induced during apoptosis and proteasomal inhibition in neuronal cells.
abstract: Neuronal apoptosis is involved in several pathological conditions of the brain. Using cDNA arrays, we observed upregulation of ubiquitin-binding protein p62 expression during serum withdrawal-induced apoptosis in Neuro-2a cells. We demonstrate here that the expression levels of p62 mRNA and protein were increased in Neuro-2a cells and cultured rat hippocampal neurons by different types of proapoptotic treatments, including serum deprivation, okadaic acid, etoposide, and trichostatin A. Ubiquitin-binding protein p62 is a widely expressed cytoplasmic protein of unclear function. The ability of p62 to bind noncovalently to ubiquitin and to several signalling proteins suggests that p62 may play a regulatory role connected to the ubiquitin system. Accordingly, we show that proteasomal inhibitors MG-132, lactacystin, and PSI caused a prominent upregulation of p62 mRNA and protein expression, with a concomitant increase in ubiquitinated proteins. To conclude, p62 upregulation appears to be a common event in neuronal apoptosis. Results also suggest that the induction of p62 expression by proteasomal inhibitors may be a response to elevated levels of ubiquitinated proteins, possibly constituting a protective mechanism.
authors.affiliation: Department of Neuroscience and Neurology, University of Kuopio, FIN-70211 Kuopio, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Kuusisto
authors.forename: T
authors.initials: T
authors.lastname: Suuronen
authors.forename: A
authors.initials: A
authors.lastname: Salminen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005047:Etoposide / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D006877:Hydroxamic Acids / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000235:genetics*; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D019319:Okadaic Acid / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D051758:Transcription Factor TFIIH; D014157:Transcription Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; D016895:Culture Media, Serum-Free; C490981:Gtf2h1 protein, mouse; D006877:Hydroxamic Acids; D017874:Immediate-Early Proteins; D009097:Multienzyme Complexes; D012333:RNA, Messenger; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; D019319:Okadaic Acid; C012589:trichostatin A; D005047:Etoposide; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex