Systemic perturbation of the ERK signaling pathway by the proteasome inhibitor, MG132.
PLoS One
; 7(11): e50975, 2012.
Article
in En
| MEDLINE
| ID: mdl-23226437
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
MAP Kinase Signaling System
/
Proteasome Inhibitors
/
Leupeptins
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2012
Document type:
Article
Affiliation country:
Estados Unidos