Eukaryotic Translation Initiation Factor 3, Subunit a, Regulates the Extracellular Signal-Regulated Kinase Pathway

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Title: Eukaryotic Translation Initiation Factor 3, Subunit a, Regulates the Extracellular Signal-Regulated Kinase Pathway
Authors: Xu, T.-R.
Lu, R.-F.
Romano, David
et al.
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Date: 24-Oct-2011
Online since: 2013-11-29T13:25:35Z
Abstract: 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.
Type of material: Journal Article
Publisher: American Society for Microbiology
Journal: Molecular and Cellular Biology
Volume: 32
Issue: 1
Start page: 88
End page: 95
Copyright (published version): 2011 American Society for Microbiology
Keywords: ERK pathwayeukaryotic translation initiation factor 3 subunit a (eIF3a)
DOI: 10.1128/MCB.05770-11
Language: en
Status of Item: Peer reviewed
Appears in Collections:SBI Research Collection

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