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

• Authors: Jian Wang, Emory University; Alton Farris III, Emory University; Kaiming Xu, Emory University; Ping Wang, Emory University; Xiangming Zhang, Emory University; Duc M. Duong, Emory University; Hong Yi, Emory University; Hui-Kuo Shu, Emory University; Shi-Yong Sun, Emory University; Ya Wang, Emory University
• Journal Title: Nature Communications
• Volume: Volume 7
• Publisher: Nature Publishing Group: Nature Communications | 2016, Pages 11795-11795
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/ncomms11795
• Subjects: Health Sciences, Oncology; Health Sciences, Radiology

Abstract

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.