Effects of RING-SH2 Grb2 , a chimeric protein containing the E3 ligase domain of Cbl, on the EGFR pathway
Journal
Chinese Journal of Physiology
Journal Volume
57
Journal Issue
6
Pages
350
Date Issued
2014-01-01
Author(s)
Abstract
© 2014 by The Chinese Physiological Society and Airiti Press Inc. The E3 ubiquitin-protein ligase Casitas B-lineage lymphoma protein (Cbl) negatively regulates epidermal growth factor receptor (EGFR) signaling pathway in many organisms, and has crucial roles in cell growth, development and human pathologies, including lung cancers. RING-SH2 Grb2 a chimeric protein of 215 amino acids containing the RING domain of Cbl that provides E3 ligase activity, and the SH2 domain of Grb2 that serves as an adaptor for EGFR. In this study, we demonstrated that RING-SH2 Grb2 could promote the ubiquitinylation and degradation of EGFR in a human non-small cell lung carcinoma cell line H1299. Moreover, we discovered that the RING-SH2 Grb2 chimera promoted the internalization of ligand-bound EGFR, inhibited the growth of H1299 cells, and significantly suppressed tumor growth in a xenograft mouse model. In summary, our results revealed a potential new cancer therapeutic approach for non-small cell lung cancer.
Subjects
c-Cbl | EGFR | Grb2 | Lung cancer | RING domain
c-Cbl; EGFR; Grb2; Lung cancer; RING domain
SDGs
Other Subjects
casitas B lineage lymphoma protein; epidermal growth factor receptor; growth factor receptor bound protein 2; protein SH2; RING finger protein; ubiquitin protein ligase E3; unclassified drug; Cbl protein; epidermal growth factor receptor; GRB2 protein, human; growth factor receptor bound protein 2; hybrid protein; mitogen activated protein kinase; animal experiment; animal model; Article; cancer growth; cancer inhibition; controlled study; down regulation; enzyme activity; enzyme degradation; enzyme repression; human; human cell; in vitro study; in vivo study; male; mouse; non small cell lung cancer; nonhuman; protein expression; signal transduction; ubiquitination; animal; Bagg albino mouse; metabolism; Neoplasms, Experimental; physiology; Src homology domain; tumor cell line; Animals; Cell Line, Tumor; Extracellular Signal-Regulated MAP Kinases; GRB2 Adaptor Protein; Humans; Male; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Proto-Oncogene Proteins c-cbl; Receptor, Epidermal Growth Factor; Recombinant Fusion Proteins; Signal Transduction; src Homology Domains
Publisher
CHINESE PHYSIOLOGICAL SOC
Type
journal article