ArticleOncogene2011
Regulation of mixed lineage kinase 3 is required for Neurofibromatosis-2-mediated growth suppression in human cancer.
Article in Oncogene, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 31 citations in OpenAlex.
- Regulation of E-cadherin by mixed lineage kinase 3 (MLK3) mediates cell adhesion in ovarian cancer spheroids.Biochimica et biophysica acta. Molecular cell research · 2026Article
- Marine Staurosporine Analogues: Activity and Target Identification in Triple-Negative Breast Cancer.Marine drugs · 2024Article
- LATS1 Regulates Mixed-Lineage Kinase 3 (MLK3) Subcellular Localization and MLK3-Mediated Invasion in Ovarian Epithelial Cells.Molecular and cellular biology · 2021Article
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
- Nicotine inhibits MAPK signaling and spheroid invasion in ovarian cancer cells.Experimental cell research · 2020Article
- Polo-like kinase 1 as a therapeutic target for malignant peripheral nerve sheath tumors (MPNST) and schwannomas.American journal of cancer research · 2020Article
- Identification of two distinct peptide-binding pockets in the SH3 domain of human mixed-lineage kinase 3.The Journal of biological chemistry · 2018Article
- MLK3 Signaling in Cancer Invasion.Cancers · 2016Review
- Article
- Merlin/NF2 Suppresses Pancreatic Tumor Growth and Metastasis by Attenuating the FOXM1-Mediated Wnt/β-Catenin Signaling.Cancer research · 2015Article
- A splicing variant of Merlin promotes metastasis in hepatocellular carcinoma.Nature communications · 2015Article
- Merlin Isoforms 1 and 2 Both Act as Tumour Suppressors and Are Required for Optimal Sperm Maturation.PloS one · 2015Article
- The E3 ligase CHIP mediates ubiquitination and degradation of mixed-lineage kinase 3.Molecular and cellular biology · 2014Article
- A neuronal function of the tumor suppressor protein merlin.Acta neuropathologica communications · 2014Review
- Targeting Cdc42 in cancer.Expert opinion on therapeutic targets · 2013Review
- Inhibition of c-Jun N-terminal kinase activity enhances vestibular schwannoma cell sensitivity to gamma irradiation.Neurosurgery · 2013Article
- Neurofibromatosis type 2 protein, NF2: an uncoventional cell cycle regulator.Anticancer research · 2013Review
- The molecular biology of vestibular schwannomas and its association with hearing loss: a review.Genetics research international · 2012Article
- Inhibition of Cdc42-mediated activation of mixed lineage kinase 3 by the tumor suppressor protein merlin.Small GTPases · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The Neurofibromatosis-2 (NF2) tumor suppressor merlin negatively regulates cell proliferation in numerous cell types. We have previously shown that the NF2 protein (merlin/schwannomin) associates with mixed lineage kinase 3 (MLK3), a mitogen-activated protein kinase (MAPK) kinase kinase that is required for the proliferation of normal and neoplastic cells. In this study, we show that merlin inhibits MLK3 activity, as well as the activation of its downstream effectors, B-Raf, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). The ability of merlin to regulate MLK3 activity requires a direct association between MLK3 and residues in the C-terminal region of merlin. Merlin integrates Rho GTPase family signaling with MAPK activity by inhibiting the binding between MLK3 and its upstream activator, Cdc42. Furthermore, we demonstrate that MLK3 is required for merlin-mediated suppression of cell proliferation and invasion. Collectively, these results establish merlin as a potent inhibitor of MLK3, ERK and JNK activation in cancer, and provide a mechanistic link between deregulated MAPK and Rho GTPase signaling in NF2 growth control.
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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.