ArticleMolecular pharmacology2017
AKT1, LKB1, and YAP1 Revealed as MYC Interactors with NanoLuc-Based Protein-Fragment Complementation Assay.
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Article in Molecular pharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 33 citations in OpenAlex.
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- Uncovering the rewired IAP-JAK regulatory axis as an immune-dependent vulnerability of LKB1-mutant lung cancer.Nature communications · 2025Article
- Evaluation of molecular glue-induced neomorphic protein-protein interaction with a cell lysate-based time-resolved fluorescence resonance energy transfer assay.ASPET discovery · 2025Article
- A multiplexed time-resolved fluorescence resonance energy transfer ultrahigh-throughput screening assay for targeting the SMAD4-SMAD3-DNA complex.Journal of molecular cell biology · 2024Article
- Targeting MYC at the intersection between cancer metabolism and oncoimmunology.Frontiers in immunology · 2024Review
- Novel Antiviral Molecules against Ebola Virus Infection.International journal of molecular sciences · 2023Article
- TMPRSS2 and SARS-CoV-2 SPIKE interaction assay for uHTS.Journal of molecular cell biology · 2023Article
- Ligand dependent interaction between PC-TP and PPARδ mitigates diet-induced hepatic steatosis in male mice.Nature communications · 2023Article
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- A time-resolved fluorescence resonance energy transfer screening assay for discovery of protein-protein interaction modulators.STAR protocols · 2021Article
- Discovery of the first chemical tools to regulate MKK3-mediated MYC activation in cancer.Bioorganic & medicinal chemistry · 2021Article
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- RP11-323N12.5 promotes the malignancy and immunosuppression of human gastric cancer by increasing YAP1 transcription.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2021Article
- Disruption of a key ligand-H-bond network drives dissociative properties in vamorolone for Duchenne muscular dystrophy treatment.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- High expression of MKK3 is associated with worse clinical outcomes in African American breast cancer patients.Journal of translational medicine · 2020Article
- Maximizing binary interactome mapping with a minimal number of assays.Nature communications · 2019Article
- Large tumor suppressor 2, LATS2, activates JNK in a kinase-independent mechanism through ASK1.Journal of molecular cell biology · 2018Article
- The OncoPPi Portal: an integrative resource to explore and prioritize protein-protein interactions for cancer target discovery.Bioinformatics (Oxford, England) · 2018Article
- Inhibition of the inflammatory response to stress by targeting interaction between PKR and its cellular activator PACT.Scientific reports · 2017Article
- Development of a Time-Resolved Fluorescence Resonance Energy Transfer Ultrahigh-Throughput Screening Assay for Targeting the NSD3 and MYC Interaction.Assay and drug development technologiesArticle
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Authors and funding
14 authors at 4 institutions in 2 countries.
Xiulei MoDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Qi QiDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Andrei A IvanovDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Qiankun NiuDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Yin LuoDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Jonathan HavelDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Russell GoetzeDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Sydney BellDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Carlos S MorenoDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Lee A D CooperDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Margaret A JohnsDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Fadlo R KhuriDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Yuhong DuDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.).
Haian FuDepartment of Pharmacology and Emory Chemical Biology Discovery Center (X.M., Q.Q., A.A.I., Q.N., Y.L., J.H., R.G., S.B., M.A.J., Y.D., H.F.) and Department of Biomedical Informatics (L.A.D.C.), Emory University School of Medicine, Atlanta, Georgia; Departments of Hematology and Medical Oncology (F.R.K., H.F.) and Pathology and Laboratory Medicine (C.S.M.) and Winship Cancer Institute, Emory University, Atlanta, Georgia; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China (Y.L.); and Department of Biomedical Engineering, Emory University School of Medicine/Georgia Institute of Technology, Atlanta, Georgia (L.A.D.C.) hfu@emory.edu.
Nanjing University · CNWinship Cancer InstituteGeorgia Institute of Technology · USEmory University · US
Funding
Winship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Suresh S Ramalingam · 2009 to 2026
$47.5MSystematic discovery of neomorph protein-protein interactions in cancer for oncogenic pathway perturbationU01CA217875 · NCI · EMORY UNIVERSITY · PI FU, HAIAN · 2017 to 2021
$4.5MHIGH THROUGHPUT PROTEIN-PROTEIN INTERACTION INTERROGATION IN CANCERU01CA168449 · NCI · EMORY UNIVERSITY · PI FU, HAIAN · 2012 to 2016
$4.2MNCI NIH HHS P30 CA138292NCI NIH HHS U01 CA168449NCI NIH HHS U01 CA217875
Abstract
The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. In this study, we report the development of a NanoLuc-based protein-fragment complementation assay (NanoPCA) and mapping of the MYC protein interaction hub in live mammalian cells. The NanoPCA system was configured to enable detection of protein-protein interactions (PPI) at the endogenous level, as shown with PRAS40 dimerization, and detection of weak interactions, such as PINCH1-NCK2. Importantly, NanoPCA allows the study of PPI dynamics with reversible interactions. To demonstrate its utility for large-scale PPI detection in mammalian intracellular environment, we have used NanoPCA to examine MYC interaction with 83 cancer-associated proteins in live cancer cell lines. Our new MYC PPI data confirmed known MYC-interacting proteins, such as MAX, GSK3A, and SMARCA4, and revealed a panel of novel MYC interaction partners, such as RAC-α serine/threonine-protein kinase (AKT)1, liver kinase B (LKB)1, and Yes-associated protein (YAP)1. The MYC interactions with AKT1, LKB1, and YAP1 were confirmed by coimmunoprecipitation of endogenous proteins. Importantly, AKT1, LKB1, and YAP1 were able to activate MYC in a transcriptional reporter assay. Thus, these vital growth control proteins may represent promising MYC regulators, suggesting new mechanisms that couple energetic and metabolic pathways and developmental signaling to MYC-regulated cellular programs.
Indexed as
Biological AssayCell Line, TumorHEK293 CellsHigh-Throughput Screening AssaysHumansLuciferasesNanoparticlesPhosphoproteinsProtein BindingProtein Interaction MappingProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-mycReproducibility of ResultsLuciferasesPhosphoproteinsProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktProto-Oncogene Proteins c-myc
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