ArticleOncogene2017
OncoPPi-informed discovery of mitogen-activated protein kinase kinase 3 as a novel binding partner of c-Myc.
Article in Oncogene, 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 40 citations in OpenAlex.
- Targeting MKK3/c-Myc interaction to overcome osimertinib acquired resistance in EGFR mutant lung cancer.Cancer letters · 2025Article
- Ubiquitin-specific protease 13 promotes colorectal cancer progression by stabilizing mitogen-activated protein kinase kinase 3.Molecular biomedicine · 2025Article
- Identification of a resistance-exercise-specific signalling pathway that drives skeletal muscle growth.Nature metabolism · 2025Article
- Uncovering the rewired IAP-JAK regulatory axis as an immune-dependent vulnerability of LKB1-mutant lung cancer.Nature communications · 2025Article
- Repurposed AT9283 triggers anti-tumoral effects by targeting MKK3 oncogenic functions in Colorectal Cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Characterization of covalent inhibitors that disrupt the interaction between the tandem SH2 domains of SYK and FCER1G phospho-ITAM.PloS one · 2024Article
- Characterization of covalent inhibitors that disrupt the interaction between the tandem SH2 domains of SYK and FCER1G phospho-ITAM.bioRxiv : the preprint server for biology · 2023Article
- Mapping oncogenic protein interactions for precision medicine.International journal of cancer · 2022Review
- Review
- A time-resolved fluorescence resonance energy transfer screening assay for discovery of protein-protein interaction modulators.STAR protocols · 2021Article
- DDIT4 S-Nitrosylation Aids p38-MAPK Signaling Complex Assembly to Promote Hepatic Reactive Oxygen Species Production.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Discovery of the first chemical tools to regulate MKK3-mediated MYC activation in cancer.Bioorganic & medicinal chemistry · 2021Article
- Expression and purification of active human kinases using Pichia pastoris as a general-purpose host.Protein expression and purification · 2021Article
- TheFrontiers in molecular neuroscience · 2021Article
- High expression of MKK3 is associated with worse clinical outcomes in African American breast cancer patients.Journal of translational medicine · 2020Article
- Online informatics resources to facilitate cancer target and chemical probe discovery.RSC medicinal chemistry · 2020Review
- Article
- In vivo screening identifies GATAD2B as a metastasis driver in KRAS-driven lung cancer.Nature communications · 2018Article
- Insights of Crosstalk between p53 Protein and the MKK3/MKK6/p38 MAPK Signaling Pathway in Cancer.Cancers · 2018Review
- The OncoPPi Portal: an integrative resource to explore and prioritize protein-protein interactions for cancer target discovery.Bioinformatics (Oxford, England) · 2018Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Mitogen-activated protein kinase kinase 3 (MKK3) is a dual threonine/tyrosine protein kinase that regulates inflammation, proliferation and apoptosis through specific phosphorylation and activation of the p38 mitogen-activated protein kinase. However, the role of MKK3 beyond p38-signaling remains elusive. Recently, we reported a protein-protein interaction (PPI) network of cancer-associated genes, termed OncoPPi, as a resource for the scientific community to generate new biological models. Analysis of the OncoPPi connectivity identified MKK3 as one of the major hub proteins in the network. Here, we show that MKK3 interacts with a large number of proteins critical for cell growth and metabolism, including the major oncogenic driver MYC. Multiple complementary approaches were used to demonstrate the direct interaction of MKK3 with MYC in vitro and in vivo. Computational modeling and experimental studies mapped the interaction interface to the MYC helix-loop-helix domain and a novel 15-residue MYC-binding motif in MKK3 (MBM). The MBM in MKK3 is distinct from the known binding sites for p38 or upstream kinases. Functionally, MKK3 stabilized MYC protein, enhanced its transcriptional activity and increased expression of MYC-regulated genes. The defined MBM peptide mimicked the MKK3 effect in promoting MYC activity. Together, the exploration of OncoPPi led to a new biological model in which MKK3 operates by two distinct mechanisms in cellular regulation through its phosphorylation of p38 and its activation of MYC through PPI.
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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.