Eukaryotic translation initiation factor 3, subunit a, regulates the extracellular signal-regulated kinase pathway

Xu, T.-R., Lu, R.-F., Romano, D., Pitt, A., Houslay, M. D., Milligan, G. and Kolch, W. (2012) Eukaryotic translation initiation factor 3, subunit a, regulates the extracellular signal-regulated kinase pathway. Molecular and Cellular Biology, 32(1), pp. 88-95. (doi: 10.1128/​MCB.05770-11)

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Publisher's URL: http://dx.doi.org/10.1128/MCB.05770-11

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 beta-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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Xu, Professor Tianrui and Houslay, Professor Miles and Kolch, Prof Walter and Pitt, Dr Andrew and Lu, Dr Ruifang and Milligan, Professor Graeme and Romano, Dr David
Authors: Xu, T.-R., Lu, R.-F., Romano, D., Pitt, A., Houslay, M. D., Milligan, G., and Kolch, W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Molecular and Cellular Biology
Publisher:American Society for Microbiology
ISSN:0270-7306
ISSN (Online):1098-5549
Published Online:28 October 2011
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