PKCepsilon binds peripherin and induces its aggregation which is accompanied by apoptosis of neuroblastoma cells.

Research output: Contribution to journalArticle

Abstract

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 PKCe 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 siRNAs targeting PKCe. PKCe and peripherin associate as shown by co-immunoprecipitation and the interaction is dependent on and mediated by the C1b domain of PKCe. The interaction was specific for PKCe since corresponding structures from other isoforms did not co-precipitate peripherin, with the exception for PKC and PKC which pulled down minute amounts. PKCe interacts with vimentin through the same structures but does not induce its aggregation. When the PKCe 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 PKCe 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 PKCe.

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Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
Original languageEnglish
Pages (from-to)16653-16664
JournalJournal of Biological Chemistry
Volume283
Issue number24
Publication statusPublished - 2008
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Tumour Cell Biology (013017530)

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