ArticleMolecular cell2022
ARAF protein kinase activates RAS by antagonizing its binding to RASGAP NF1.
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Article in Molecular cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14citing papers in PubMed
1.7field-weighted citation impact, top 15% of its field
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- A‑Raf: A serine/threonine protein kinase with important biological functions (Review).Molecular medicine reports · 2026Review
- ARAF regulates malignant progression of bladder cancer through the p38MAPK pathway.Open medicine (Warsaw, Poland) · 2026Article
- Inflammation awakens dormant cancer cells by modulating the epithelial-mesenchymal phenotypic state.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- RAS signaling gets granular.Nature chemical biology · 2025Article
- Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance.Nature chemical biology · 2025Article
- Article
- Tumor biomarkers for diagnosis, prognosis and targeted therapy.Signal transduction and targeted therapy · 2024Review
- Targeting RAF dimers in RAS mutant tumors: From biology to clinic.Acta pharmaceutica Sinica. B · 2024Review
- BRAF - a tumour-agnostic drug target with lineage-specific dependencies.Nature reviews. Clinical oncology · 2024Review
- Article
- Platycodin D represses β-catenin to suppress metastasis of cetuximab-treated KRAS wild-type colorectal cancer cells.Clinical & experimental metastasis · 2023Article
- RAF1 contributes to cell proliferation and STAT3 activation in colorectal cancer independently of microsatellite and KRAS status.Oncogene · 2023Article
- Rare molecular subtypes of lung cancer.Nature reviews. Clinical oncology · 2023Review
- Dynamic regulation of RAS and RAS signaling.The Biochemical journal · 2023Article
Corrections and comments
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Authors and funding
27 authors at 9 institutions in 3 countries.
Wenjing SuMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Radha MukherjeeMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Rona YaegerDepartment of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jieun SonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Jianing XuMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Na NaMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Neilawattie Merna TimaulMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jaclyn HechtmanDepartment of Pathology, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Viktoriya ParoderDepartment of Radiology, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Mika LinDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Marissa MattarMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Juan QiuMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Qing ChangMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Huiyong ZhaoMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Jonathan ZhangMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Megan LittleMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Yuta AdachiDivision of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan.
Sae-Won HanUCSF Helen Diller Family Comprehensive Cancer Center, School of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Internal Medicine, Seoul National University Hospital, Seoul, 03080, South Korea.
Barry S TaylorDepartment of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065, USA; Marie-Josee and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Discovery and Applied Genomics, Loxo Oncology at Lilly, Stamford, CT 06901, USA.
Hiromichi EbiDivision of Molecular Therapeutics, Aichi Cancer Center Research Institute, Nagoya, 464-8681, Japan; Division of Advanced Cancer Therapeutics, Nagoya University Graduate School of Medicine, Nagoya, 466-8650, Japan.
Omar Abdel-WahabDepartment of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY 10065, USA.
Elisa de StanchinaMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Charles M RudinDepartment of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Pasi A JänneDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Harvard Medical School, Boston, MA 02215, USA.
Frank McCormickUCSF Helen Diller Family Comprehensive Cancer Center, School of Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Frederick, MD 21701, USA.
Zhan YaoMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Mechanistic Biology, Loxo Oncology at Lilly, New York, NY 10016, USA. Electronic address: zyao@loxooncology.com.
Neal RosenMolecular Pharmacology Program, Sloan Kettering Institute for Cancer Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: rosenn@mskcc.org.
Memorial Sloan Kettering Cancer Center · USMemorial Hospital · USDana-Farber Cancer Institute · USAichi Cancer Center · JPFrederick National Laboratory for Cancer Research · USHarvard University · USLoxo Oncology at Lilly (United States) · USNagoya University · JPUniversity of California, San Francisco · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4MThe Role of Id Proteins in Breast TumorigenesisP01CA094060 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI NORTON, LARRY · 2002 to 2018
$39.4MMSKCC Pilot Center for Precision Disease ModelingU54OD020355 · OD · SLOAN-KETTERING INST CAN RESEARCH · PI LOWE, SCOTT W., SOLIT, DAVID B. · 2015 to 2019
$9.9MStudies on oncoprotein-induced feedback: Basic and therapeutic implicationsR35CA210085 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ROSEN, NEAL · 2016 to 2022
$7.3MDevelopment of Combination Therapies to Delay/Prevent Acquired Drug ResistanceR35CA220497 · NCI · DANA-FARBER CANCER INST · PI JANNE, PASI A · 2018 to 2024
$7.2MIdentification and validation of synthetic lethality in KRAS mutant lung adenocarcinoma patient derived xenograftsU01CA199215 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI POIRIER, JOHN THOMAS, RUDIN, CHARLES M. · 2015 to 2019
$2.7MOrigins of BRAF-mutant hematologic malignancies and their therapeutic resistanceR01CA201247 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI ABDEL-WAHAB, OMAR, PARK, CHRISTOPHER Y · 2016 to 2020
$2.7MExploiting the distinct genomics and signaling of colorectal cancers to effectively target ERKR01CA233736 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI YAEGER, RONA · 2019 to 2024
$2.5MUnderstanding Long Tail Driver Mutations in CancerR01CA204749 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SCHULTZ, NIKOLAUS · 2017 to 2021
$2.0MTargeting AKT-Mutant Human CancersR01CA207244 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI SOLIT, DAVID B. · 2016 to 2020
$2.0MNCI NIH HHS P01 CA094060NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA201247NCI NIH HHS R01 CA204749NCI NIH HHS R01 CA207244NCI NIH HHS R01 CA233736NCI NIH HHS R35 CA210085NCI NIH HHS R35 CA220497NCI NIH HHS U01 CA199215NIH HHS U54 OD020355
Abstract
RAF protein kinases are effectors of the GTP-bound form of small guanosine triphosphatase RAS and function by phosphorylating MEK. We showed here that the expression of ARAF activated RAS in a kinase-independent manner. Binding of ARAF to RAS displaced the GTPase-activating protein NF1 and antagonized NF1-mediated inhibition of RAS. This reduced ERK-dependent inhibition of RAS and increased RAS-GTP. By this mechanism, ARAF regulated the duration and consequences of RTK-induced RAS activation and supported the RAS output of RTK-dependent tumor cells. In human lung cancers with EGFR mutation, amplification of ARAF was associated with acquired resistance to EGFR inhibitors, which was overcome by combining EGFR inhibitors with an inhibitor of the protein tyrosine phosphatase SHP2 to enhance inhibition of nucleotide exchange and RAS activation.
Indexed as
Neurofibromin 1Proto-Oncogene Proteins A-rafras GTPase-Activating ProteinsErbB ReceptorsGuanosine TriphosphateHumansProtein BindingSignal TransductionErbB ReceptorsGuanosine TriphosphateNeurofibromin 1NF1 protein, humanProto-Oncogene Proteins A-rafras GTPase-Activating ProteinsARAFdrug sensitivityERK signalingNF1RAS-GTPreceptor tyrosine kinase inhibitor
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.