Effects of RING-SH2 Grb2 , a chimeric protein containing the E3 ligase domain of Cbl, on the EGFR pathway

Wei Hao Lee, Pei Yu Wang, Yu Hung Lin, He Yen Chou, Yen Hsien Lee, Chien Kuo Lee, Li Mei Pai*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)350-357
頁數8
期刊Chinese Journal of Physiology
57
發行號6
DOIs
出版狀態已出版 - 2014

文獻附註

Publisher Copyright:
© 2014 by The Chinese Physiological Society and Airiti Press Inc.

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