ArticleNeoplasia (New York, N.Y.)2011
Multistep phosphorylation by oncogenic kinases enhances the degradation of the NF2 tumor suppressor merlin.
Article in Neoplasia (New York, N.Y.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Harnessing the FGFR2/NF2/YAP signaling-dependent necroptosis to develop an FGFR2/IL-8 dual blockade therapeutic strategy.Nature communications · 2025Article
- The molecular biology of NF2/Merlin on tumorigenesis and development.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.Cell death & disease · 2024Article
- The genetic landscape and possible therapeutics of neurofibromatosis type 2.Cancer cell international · 2023Review
- Article
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- TNIK Is a Therapeutic Target in Lung Squamous Cell Carcinoma and Regulates FAK Activation through Merlin.Cancer discovery · 2021Article
- Chronic shisha exposure alters phosphoproteome of oral keratinocytes.Journal of cell communication and signaling · 2019Article
- Phosphorylation of Merlin by Aurora A kinase appears necessary for mitotic progression.The Journal of biological chemistry · 2019Article
- Two Sides of the Coin: Ezrin/Radixin/Moesin and Merlin Control Membrane Structure and Contact Inhibition.International journal of molecular sciences · 2019Review
- Role of Merlin/NF2 inactivation in tumor biology.Oncogene · 2016Review
- Schwannomas and their pathogenesis.Brain pathology (Zurich, Switzerland) · 2014Review
- The hippo pathway is activated and is a causal mechanism for adipogenesis in arrhythmogenic cardiomyopathy.Circulation research · 2014Article
- NF2/merlin in hereditary neurofibromatosis 2 versus cancer: biologic mechanisms and clinical associations.Oncotarget · 2014Review
- Cancer subclonal genetic architecture as a key to personalized medicine.Neoplasia (New York, N.Y.) · 2013Article
- Overcoming intratumor heterogeneity of polygenic cancer drug resistance with improved biomarker integration.Neoplasia (New York, N.Y.) · 2012Article
- Merlin: the wizard requires protein stability to function as a tumor suppressor.Biochimica et biophysica acta · 2012Review
- Distinct overlapping sequences at the carboxy-terminus of merlin regulate its tumour suppressor and morphogenic activity.Journal of cellular and molecular medicine · 2012Article
- Molecular mechanisms promoting the pathogenesis of Schwann cell neoplasms.Acta neuropathologica · 2012Review
- The molecular biology of vestibular schwannomas and its association with hearing loss: a review.Genetics research international · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the Neurofibromatosis 2 gene (NF2) predispose to tumors of the nervous system, mainly schwannomas and meningiomas. The NF2 gene encodes for the tumor suppressor protein merlin (moesin-ezrin-radixin-like protein), which functions as a linker between the plasma membrane and the cytoskeleton. Carboxyterminal phosphorylation affects merlin activity, but many open questions on the regulation of merlin function still remain. The phosphoinositide 3-kinase/Akt pathway is activated in human vestibular schwannoma, suggesting a role for Akt-dependent merlin regulation in the formation of these tumors. In this study, we identify merlin serine 10 as a novel substrate for Akt phosphorylation. We demonstrate that this N-terminal phosphorylation directs merlin for proteasome-mediated degradation and affects merlin binding to the E3 ligase component DCAF1. Our data indicate that sequential phosphorylation of merlin C- and N-terminus by different oncogenic kinases targets merlin for degradation and thus downregulates its activity. On the basis of these findings, we propose a model for a posttranslational mechanism of merlin inactivation.
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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.