Eukaryotic Translation Initiation Factor 3, Subunit a, Regulates the Extracellular Signal-Regulated Kinase Pathway
The Translation Factor eIF3a Regulates the Extracellular Signal regulated Kinase (ERK) Pathway
24 October 2011
29T13:25:35Z November 2013
The extracellular signal-regulated kinase (ERK) pathway participates in the control of numerous cellular processes, including cell proliferation. Since its activation kinetics are critical for to its biological effects, they are tightly regulated. We report that the protein translation factor, eukaryotic translation initiation factor 3, subunit a (eIF3a), binds to SHC and Raf-1, two components of the ERK pathway. The interaction of eIF3a with Raf-1 is increased by β-arrestin2 expression and transiently decreased by epidermal growth factor (EGF) stimulation in a concentration-dependent manner. The EGF-induced decrease in Raf-1–eIF3a association kinetically correlates with the time course of ERK activation. eIF3a interferes with Raf-1 activation and eIF3a downregulation by small interfering RNA enhances ERK activation, early gene expression, DNA synthesis, expression of neuronal differentiation markers in PC12 cells, and Ras-induced focus formation in NIH 3T3 cells. Thus, eIF3a is a negative modulator of ERK pathway activation and its biological effects.
This study was supported by Medical Research Council grant G0400053/69186 and by Science Foundation Ireland under grant 06/CE/B1129.
Type of Material
American Society for Microbiology
Molecular and Cellular Biology
Copyright (Published Version)
2011 American Society for Microbiology
Status of Item
This item is made available under a Creative Commons License