Systematic Identification of Oncogenic EGFR Interaction Partners

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• 作者：Julia Petschnigg¹ ; Max Kotlyar² ; Louise Blair¹ ; Igor Jurisica² ; ³ ; ⁴ ; ⁵ ; Igor Stagljar⁶ ; ⁷ ; ⁸ ; Robin Ketteler¹ ; ^{r.ketteler@ucl.ac.uk}
• 关键词：EGF ; epidermal growth factor ; EGFR ; epidermal growth factor receptor ; ERK ; extracellular signal-regulated kinase ; GFP ; green fluorescent protein ; Grb2 ; growth factor receptor-bound protein 2 ; SH ; Src homology ; MAPK ; mitogen-activated protein kinase ; TK ; tyrosine kinase ; TKI ; TK inhibitor ; NSCLC ; non-small cell lung cancer ; MaMTH ; mammalian membrane two-hybrid ; TACC ; transforming acidic coiled-coil protein ; GO ; gene ontology ; Cub ; C-terminal half of ubiquitin ; TF ; transcription factor ; Nub ; N-ter
• 刊名：Journal of Molecular Biology
• 出版年：2017
• 出版时间：20 January 2017
• 年：2017
• 卷：429
• 期：2
• 页码：280-294
• 全文大小：1532 K
• 卷排序：429

文摘

A combined screening approach involving an image-based green fluorescent protein-Grb2 translocation assay and a mammalian membrane two-hybrid protein–protein interaction assay identified 11 novel interactors of EGFR. Eight of those were further confirmed by co-immunoprecipitation. TACC3 was identified as a novel EGFR interactor, which specifically binds to oncogenic EGFR variants. TACC3 directly modulates EGFR stability at the cell surface and hence promotes mitogen-activated protein kinase signaling. Targeting TACC3 in non-small cell lung cancer cells partially resensitizes TK-resistant cells to TK inhibitors.