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Author Notes:

Email: ywang94@emory.edu

J.W. performed most experiments including plasmid constructs, IP, immunofluorescence, western blot, real-time PCR and so on. J.W. was also involved in the data analysis and writing of this manuscript. K.X. and H.-K.S. helped perform the [35S] methionine–cysteine incorporation and polysomal distribution experiments. D.M.D. performed the quantitative global proteomics using mTRAQ labelling experiments and analysed the related data. H.Y. performed the immuno-transmission electron microscopy experiments.

P.W. and X.Z. performed the mice irradiation and lung tissue collection. A.B.F. was involved in identifying lung tumours by examining the mice lung tissue slides. S.-Y.S. was involved in the experiment design and manuscript writing. Y.W. designed this study and wrote this manuscript.

We thank Doreen Theune for editing this manuscript.


Research Funding:

This work is supported by grants from the NASA (NNX11AC30G) and NIH (CA186129, CA185882, 1S10RR-025679-01 and P30CA138292).

GPRC5A suppresses protein synthesis at the endoplasmic reticulum to prevent radiation-induced lung tumorigenesis.

Journal Title:

Nature Communications


Volume 7


, Pages 11795-11795

Type of Work:

Article | Final Publisher PDF


GPRC5A functions as a lung tumour suppressor to prevent spontaneous and environmentally induced lung carcinogenesis; however, the underlying mechanism remains unclear. Here we reveal that GPRC5A at the endoplasmic reticulum (ER) membrane suppresses synthesis of the secreted or membrane-bound proteins including a number of oncogenes, the most important one being Egfr. The ER-located GPRC5A disturbs the assembly of the eIF4F-mediated translation initiation complex on the mRNA cap through directly binding to the eIF4F complex with its two middle extracellular loops. Particularly, suppression of EGFR by GPRC5A contributes significantly to preventing ionizing radiation (IR)-induced lung tumorigenesis. Thus, GPRC5A deletion enhances IR-promoted EGFR expression through an increased translation rate, thereby significantly increasing lung tumour incidence in Gprc5a(-/-) mice. Our findings indicate that under-expressed GPRC5A during lung tumorigenesis enhances any transcriptional stimulation through an active translational status, which can be used to control oncogene expression and potentially the resulting related disease.

Copyright information:

© 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/).

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