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

Sunesson, Lovisa LU ; Hellman, Ulf and Larsson, Christer LU (2008) In Journal of Biological Chemistry 283(24). p.16653-16664
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
283
issue
24
pages
16653 - 16664
publisher
ASBMB
external identifiers
  • wos:000256497100042
  • pmid:18408015
  • scopus:47749116917
ISSN
1083-351X
DOI
10.1074/jbc.M710436200
language
English
LU publication?
yes
id
aa199123-58ba-487e-9965-b9fee1adbbee (old id 1147414)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18408015?dopt=Abstract
date added to LUP
2008-05-07 13:52:43
date last changed
2017-01-01 05:08:14
@article{aa199123-58ba-487e-9965-b9fee1adbbee,
  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.},
  author       = {Sunesson, Lovisa and Hellman, Ulf and Larsson, Christer},
  issn         = {1083-351X},
  language     = {eng},
  number       = {24},
  pages        = {16653--16664},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {PKCepsilon binds peripherin and induces its aggregation which is accompanied by apoptosis of neuroblastoma cells.},
  url          = {http://dx.doi.org/10.1074/jbc.M710436200},
  volume       = {283},
  year         = {2008},
}