Premium
Activation of PERK kinase in neural cells by proteasome inhibitor treatment
Author(s) -
Zhang Le,
Ebenezer Philip J.,
Dasuri Kalavathi,
BruceKeller Annadora J.,
FernandezKim Sun Ok,
Liu Ying,
Keller Jeffrey N.
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06448.x
Subject(s) - proteasome , proteasome inhibitor , microbiology and biotechnology , kinase , endoplasmic reticulum , eif 2 kinase , protein kinase a , p38 mitogen activated protein kinases , biology , unfolded protein response , cyclin dependent kinase 2
J. Neurochem. (2010) 112 , 238–245. Abstract Inhibition of the proteasome proteolytic pathway occurs as the result of normal aging, as well as in a variety of neurodegenerative conditions, and is believed to promote cellular toxicity in each of these conditions through diverse mechanisms. In the present study, we examined whether proteasome inhibition alters the protein kinase receptor‐like endoplasmic reticulum kinase (PERK). Our studies demonstrate that proteasome inhibitors induce the transient activation of PERK in both primary rat neurons as well as the N2a neural cell line. Experiments with siRNA to PERK demonstrated that the modulation of PERK was not significant involved in regulating toxicity, ubiquitinated protein levels, or ribosome perturbations in response to proteasome inhibitor treatment. Surprisingly, PERK was observed to be involved in the up‐regulation of p38 kinase following proteasome inhibitor treatment. Taken together, these data demonstrate the ability of proteasome inhibition to activate PERK and demonstrate evidence for novel cross‐talk between PERK and the activation of p38 kinase in neural cells following proteasome inhibition. Taken together, these data have implications for understanding the basis by which proteasome inhibition alters neural homeostasis, and the basis by which cell signaling cascades are regulated by proteasome inhibition.