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...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3511445?pdf=render |
| _version_ | 1818552840211136512 |
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| author | Murat Cirit Kyle G Grant Jason M Haugh |
| author_facet | Murat Cirit Kyle G Grant Jason M Haugh |
| author_sort | Murat Cirit |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T09:18:20Z |
| format | Article |
| id | doaj.art-c7ef058983d2475d8dca1f1923c15a73 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T09:18:20Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c7ef058983d2475d8dca1f1923c15a732022-12-22T00:29:18ZengPublic 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 |
| spellingShingle | Murat Cirit Kyle G Grant Jason M Haugh Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132. PLoS ONE |
| title | 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_short | 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 |
| url | http://europepmc.org/articles/PMC3511445?pdf=render |
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