Protein kinase C epsilon binds peripherin and induces its aggregation, which is accompanied by apoptosis of neuroblastoma cells.
2008 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, Vol. 283, no 24, 16653-16664 p.Article in journal (Refereed) Published
A hallmark of the afflicted nervous tissue in amyotrophic lateral sclerosis is the presence of protein aggregates, which to a large extent contain the intermediate filament protein peripherin. Here we show that activation of protein kinase C (PKC) or overexpression of PKC epsilon induces the aggregation of peripherin in cultured neuroblastoma cells with elevated amounts of peripherin. The formation of aggregates was coupled to an increased apoptosis, suggesting a functional link between these events. Both induction of aggregates and apoptosis were suppressed in cells that had been transfected with small interfering RNAs targeting PKC epsilon. PKC epsilon and peripherin associate as shown by co-immunoprecipitation, and the interaction is dependent on and mediated by the C1b domain of PKC epsilon. The interaction was specific for PKC epsilon since corresponding structures from other isoforms did not co-precipitate peripherin, with the exception for PKC eta and-theta, which pulled down minute amounts. PKC epsilon interacts with vimentin through the same structures but does not induce its aggregation. When the PKC epsilon C1b domain is expressed in neuroblastoma cells together with peripherin, both phorbol ester-induced peripherin aggregation and apoptosis are abolished, supporting a model in which PKC epsilon through its interaction with peripherin facilitates its aggregation and subsequent cell death. These events may be prevented by expressing molecules that bind peripherin at the same site as PKC epsilon.
Place, publisher, year, edition, pages
2008. Vol. 283, no 24, 16653-16664 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-110160DOI: 10.1074/jbc.M710436200ISI: 000256497100042PubMedID: 18408015OAI: oai:DiVA.org:uu-110160DiVA: diva2:275466