Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132.

Inhibition of the ubiquitin-proteasome protein degradation pathway has been identified as a viable strategy for anti-tumor therapy based on its broad effects on cell proliferation. By the same token, the variety of elicited effects confounds the interpretation of cell-based experiments using proteas...

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Main Authors: Murat Cirit, Kyle G Grant, Jason M Haugh
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3511445?pdf=render
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spelling doaj-c7ef058983d2475d8dca1f1923c15a732020-11-25T00:23:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01711e5097510.1371/journal.pone.0050975Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132.Murat CiritKyle G GrantJason M HaughInhibition of the ubiquitin-proteasome protein degradation pathway has been identified as a viable strategy for anti-tumor therapy based on its broad effects on cell proliferation. By the same token, the variety of elicited effects confounds the interpretation of cell-based experiments using proteasome inhibitors such as MG132. It has been proposed that MG132 treatment reduces growth factor-stimulated phosphorylation of extracellular signal-regulated kinases (ERKs), at least in part through upregulation of dual specificity phosphatases (DUSPs). Here, we show that the effects of MG132 treatment on ERK signaling are more widespread, leading to a reduction in activation of the upstream kinase MEK. This suggests that MG132 systemically perturbs the intracellular phosphoproteome, impacting ERK signaling by reducing phosphorylation status at multiple levels of the kinase cascade.http://europepmc.org/articles/PMC3511445?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Murat Cirit
Kyle G Grant
Jason M Haugh
spellingShingle Murat Cirit
Kyle G Grant
Jason M Haugh
Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132.
PLoS ONE
author_facet Murat Cirit
Kyle G Grant
Jason M Haugh
author_sort Murat Cirit
title Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132.
title_short Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132.
title_full Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132.
title_fullStr Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132.
title_full_unstemmed Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132.
title_sort systemic perturbation of the erk signaling pathway by the proteasome inhibitor, mg132.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2012-01-01
description Inhibition of the ubiquitin-proteasome protein degradation pathway has been identified as a viable strategy for anti-tumor therapy based on its broad effects on cell proliferation. By the same token, the variety of elicited effects confounds the interpretation of cell-based experiments using proteasome inhibitors such as MG132. It has been proposed that MG132 treatment reduces growth factor-stimulated phosphorylation of extracellular signal-regulated kinases (ERKs), at least in part through upregulation of dual specificity phosphatases (DUSPs). Here, we show that the effects of MG132 treatment on ERK signaling are more widespread, leading to a reduction in activation of the upstream kinase MEK. This suggests that MG132 systemically perturbs the intracellular phosphoproteome, impacting ERK signaling by reducing phosphorylation status at multiple levels of the kinase cascade.
url http://europepmc.org/articles/PMC3511445?pdf=render
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