ArticleCell2022
Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
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Article in Cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40citing papers in PubMed
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40 citing papers in PubMed, 71 citations in OpenAlex.
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- Variant characterization in the intrinsically disordered human proteome.Nature structural & molecular biology · 2026Article
- Discovery of molecular glues that bind FKBP12 and structurally distinct targets using DNA-encoded libraries.Nature communications · 2026Article
- Proteoform medicine: characterizing and targeting protein forms in human disease.Nature reviews. Genetics · 2026Review
- Neo-Cysteine Molecular Glues for Targeting Mutated SMAD4 Protein.Angewandte Chemie (International ed. in English) · 2026Article
- Identification and characterization of BRAF⇔TP53 interactions in melanoma.Cell reports · 2026Article
- From Serendipity to Strategy: Rationalizing Molecular Glue Discovery and Proximity-Induced Pharmacology through Chemical Biology.Journal of the American Chemical Society · 2026Review
- Pan-cancer inference and validation of hypermorphic, hypomorphic and neomorphic mutations.Nature genetics · 2026Article
- Identification and characterization of a TGF-β-independent SMAD4-NFATc1-STAT3 regulatory axis.Journal of molecular cell biology · 2026Article
- Clues for glues: from serendipity to nature's blueprints in degrader discovery.Essays in biochemistry · 2025Review
- Navigating Drug Discovery for Myhre Syndrome: The Complexity of a Multisystemic Rare Disease.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Review
- STING inhibits the progression of esophageal squamous cell carcinoma by suppressing CPT1A-mediated fatty acid β-oxidation.Acta pharmacologica Sinica · 2025Article
- When neighbors play a role: A systems-level analysis of protein interactions conditioning cancer driver mutation effects.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Pseudorabies virus induces ferroptosis by disrupting iron homeostasis through activation of TfR1 and ferritinophagy.Journal of virology · 2025Article
- The coming era of proteomics-driven precision medicine.National science review · 2025Review
- Targeted protein degradation for cancer therapy.Nature reviews. Cancer · 2025Review
- Spatially resolved subcellular protein-protein interactomics in drug-perturbed lung-cancer cultures and tissues.Nature biomedical engineering · 2025Article
- Optimization and development of a high-throughput TR-FRET screening assay for SLIT2/ROBO1 interaction.SLAS discovery : advancing life sciences R & D · 2025Article
- Lymphatic Metastasis of Esophageal Squamous Cell Carcinoma: The Role of NRF2 and Therapeutic Strategies.Cancers · 2025Review
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Authors and funding
24 authors at 4 institutions in 3 countries.
Xiulei MoDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Qiankun NiuDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Andrey A IvanovDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Yiu Huen TsangDivision of Oncologic Science, Oregon Health Sciences University School of Medicine, Portland, OR 97239, USA.
Cong TangDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Urology, The First Affiliated Hospital, Medical School of Xi'An Jiaotong University, Xi'an, Shannxi 710061, PRC.
Changfa ShuDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Gynecology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, PRC.
Qianjin LiDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Kun QianDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Alafate WahafuDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Neurosurgery, the First Affiliated Hospital of Xi'An Jiaotong University, Xi'an, PRC.
Sean P DoyleDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Danielle CickaDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Xuan YangDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Dacheng FanDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Matthew A ReynaDepartment of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Lee A D CooperDepartment of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Carlos S MorenoWinship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Wei ZhouDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA.
Taofeek K OwonikokoDepartment of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA.
Sagar LonialDepartment of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA.
Fadlo R KhuriDepartment of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA; Department of Internal Medicine, Division of Hematology and Oncology, American University of Beirut, Beirut, 1107-2020, Lebanon.
Yuhong DuDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Suresh S RamalingamWinship Cancer Institute of Emory University, Atlanta, GA 30322, USA.
Gordon B MillsDivision of Oncologic Science, Oregon Health Sciences University School of Medicine, Portland, OR 97239, USA.
Haian FuDepartment of Pharmacology and Chemical Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Emory Chemical Biology Discovery Center, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA; Department of Hematology and Medical Oncology, Emory University, Atlanta, GA 30322, USA. Electronic address: hfu@emory.edu.
Emory University · USOregon Health & Science University · USCentral South University · CNNorthwestern University · US
Funding
Implementing a Maternal health and PRegnancy Outcomes Vision for Everyone (IMPROVE)UL1TR002378 · NCATS · EMORY UNIVERSITY · PI Andres J Garcia, Elizabeth O. Ofili · 2017 to 2026
$92.1MWinship Cancer Institute Cancer Center Support GrantP30CA138292 · NCI · EMORY UNIVERSITY · PI Suresh S Ramalingam · 2009 to 2026
$47.5MProject 3: Targeting Bax signaling to overcome treatment resistance in NSCLCP50CA217691 · NCI · EMORY UNIVERSITY · PI DENG, XINGMING · 2019 to 2024
$10.1MGraduate Training in the Pharmacological StudiesT32GM008602 · NIGMS · EMORY UNIVERSITY · PI HALL, RANDY A. · 1996 to 2021
$5.1MSystematic discovery of neomorph protein-protein interactions in cancer for oncogenic pathway perturbationU01CA217875 · NCI · EMORY UNIVERSITY · PI FU, HAIAN · 2017 to 2021
$4.5MIntegrative bioinformatics and functional characterization of oncogenic driver aberrations in cancerU01CA217842 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DENEEN, BENJAMIN, MILLS, GORDON B. · 2017 to 2021
$3.6MNCATS NIH HHS UL1 TR002378NCI NIH HHS P30 CA138292NCI NIH HHS P50 CA217691NCI NIH HHS U01 CA217842NCI NIH HHS U01 CA217875NIGMS NIH HHS T32 GM008602
Abstract
Comprehensive sequencing of patient tumors reveals genomic mutations across tumor types that enable tumorigenesis and progression. A subset of oncogenic driver mutations results in neomorphic activity where the mutant protein mediates functions not engaged by the parental molecule. Here, we identify prevalent variant-enabled neomorph-protein-protein interactions (neoPPI) with a quantitative high-throughput differential screening (qHT-dS) platform. The coupling of highly sensitive BRET biosensors with miniaturized coexpression in an ultra-HTS format allows large-scale monitoring of the interactions of wild-type and mutant variant counterparts with a library of cancer-associated proteins in live cells. The screening of 17,792 interactions with 2,172,864 data points revealed a landscape of gain of interactions encompassing both oncogenic and tumor suppressor mutations. For example, the recurrent BRAF V600E lesion mediates KEAP1 neoPPI, rewiring a BRAF
Indexed as
NeoplasmsProto-Oncogene Proteins B-rafCarcinogenesisHumansKelch-Like ECH-Associated Protein 1MutationNF-E2-Related Factor 2Kelch-Like ECH-Associated Protein 1NF-E2-Related Factor 2Proto-Oncogene Proteins B-rafBRET(n)cancer genomicscancer targetdriver mutationsinteractomeneoPPIoncogeneprotein-protein interactionsystems biologytumor suppressor
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