ArticleOncogene2018
The dimer-dependent catalytic activity of RAF family kinases is revealed through characterizing their oncogenic mutants.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
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Who cites it
36 citing papers in PubMed, 58 citations in OpenAlex.
- Langerhans cell histiocytosis: molecular mechanisms underlying pathogenesis and emerging targeted therapeutics.Cancer metastasis reviews · 2026Review
- Decoding the Raf-Mek-Erk-Rsk pathway in prostate cancer: from molecular mechanisms to clinical opportunities.British journal of cancer · 2026Review
- MEK interactions tune RAF kinase sensitivity to conformation-selective inhibition.Nature chemical biology · 2026Article
- BRAF mutation and tumor immune microenvironment in new era.American journal of cancer research · 2026Review
- Exploring the pathway: clinical utility and open challenges of targeting BRAF alterations in biliary tract cancers and gastrointestinal malignancies.ESMO gastrointestinal oncology · 2025Review
- Oncogenic non-V600 mutations evade the regulatory machinery of RAF including the Cdc37/Hsp90 chaperone and the 14-3-3 scaffold.Theranostics · 2025Article
- Metabolism: an important player in glioma survival and development.Discover oncology · 2024Review
- Therapeutic vulnerabilities and pan-cancer landscape of BRAF class III mutations in epithelial solid tumors.BJC reports · 2024Article
- Targeting RAF dimers in RAS mutant tumors: From biology to clinic.Acta pharmaceutica Sinica. B · 2024Review
- Live-cell target engagement of allosteric MEKi on MEK-RAF/KSR-14-3-3 complexes.Nature chemical biology · 2024Article
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- FGFR blockade inhibits targeted therapy-tolerant persister in basal FGFR1- and FGF2-high cancers with driver oncogenes.NPJ precision oncology · 2023Article
- BRAFScience advances · 2023Article
- RAS-independent ERK activation by constitutively active KSR3 in non-chordate metazoa.Nature communications · 2023Article
- Analysis of RAS and drug induced homo- and heterodimerization of RAF and KSR1 proteins in living cells using split Nanoluc luciferase.Cell communication and signaling : CCS · 2023Article
- Selected Approaches to Disrupting Protein-Protein Interactions within the MAPK/RAS Pathway.International journal of molecular sciences · 2023Review
- Activation mechanisms of clinically distinct B-Raf V600E and V600K mutants.Cancer communications (London, England) · 2023Article
- Multidrug resistance in the standardized treatment of colon cancer harboring a rare fibrosarcoma B-type (BRAF) p.N581I mutation: a case report.Frontiers in oncology · 2023Article
- Targeting RAS-RAF-MEK-ERK signaling pathway in human cancer: Current status in clinical trials.Genes & diseases · 2023Review
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Although extensively studied for three decades, the molecular mechanisms that regulate the RAF/MEK/ERK kinase cascade remain ambiguous. Recent studies identified the dimerization of RAF as a key event in the activation of this cascade. Here, we show that in-frame deletions in the β3-αC loop activate ARAF as well as BRAF and other oncogenic kinases by enforcing homodimerization. By characterizing these RAF mutants, we find that ARAF has less allosteric and catalytic activity than the other two RAF isoforms, which arises from its non-canonical APE motif. Further, these RAF mutants exhibit a strong oncogenic potential, and a differential inhibitor resistance that correlates with their dimer affinity. Using these unique mutants, we demonstrate that active RAFs, including the BRAF(V600E) mutant, phosphorylate MEK in a dimer-dependent manner. This study characterizes a special category of oncogenic kinase mutations, and elucidates the molecular basis that underlies the differential ability of RAF isoforms to stimulate MEK-ERK pathway. Further, this study reveals a unique catalytic feature of RAF family kinases that can be exploited to control their activities for cancer therapies.
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Registered trials
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 OpenQuestion graph.