MOL Highlight: AKT1, LKB1, and YAP1 Revealed as MYC Interactors with NanoLuc-Based Protein-Fragment Complementation Assay
The c-Myc transcription factor is a major cancer driver, but the identification of small molecules that selectively target this protein has been challenging. An alternative strategy for the development of c-Myc directed cancer chemotherapeutics is to target its interaction partners. In this study, a novel protein-fragment complementation assay (NanoPCA) was developed to map the MYC protein interaction hub in live mammalian cells with proteins expressed at endogenous levels. The assay allows the study of weak protein-protein interaction dynamics and reversible interactions. NanoPCA was then used to examine c-Myc interactions with 83 cancer-associated proteins in live cancer cell lines. The results confirm known c-Myc-interaction proteins, as well as a panel of novel partners, such as RAC-α serine/threonine-protein kinase (AKT)1, liver kinase B (LKB)1, and Yes-associated protein (YAP)1. Importantly, AKT1, LKB1, and YAP1 were able to activate c-Myc in a transcriptional reporter assay. The identification of these vital growth control proteins by NanoPCA suggests new linkages between energetic, metabolic, and developmental signaling pathways and c-Myc-regulated transcription.
See the article by Mo et al. at Molecular Pharmacology April 2017, 91 (4) 339-347; DOI: https://doi.org/10.1124/mol.116.107623