ArticleMolecular and cellular biology2010
The RasGAP proteins Ira2 and neurofibromin are negatively regulated by Gpb1 in yeast and ETEA in humans.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 59 citations in OpenAlex.
- Global proteomics and affinity mass spectrometry analysis of human Schwann cells indicates that variation in and loss of neurofibromin (NF1) alters protein expression and cellular and mitochondrial metabolism.Scientific reports · 2025Article
- Exploring the role of ubiquitin regulatory X domain family proteins in cancers: bioinformatics insights, mechanisms, and implications for therapy.Journal of translational medicine · 2024Review
- Article
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Article
- Identification of Germinal Neurofibromin Hotspots.Biomedicines · 2022Article
- Deubiquitinase Ubp3 regulates ribophagy and deubiquitinates Smo1 for appressorium-mediated infection by Magnaporthe oryzae.Molecular plant pathology · 2022Article
- Enzymes in the Cholesterol Synthesis Pathway: Interactomics in the Cancer Context.Biomedicines · 2021Article
- Multi-omics analysis of glucose-mediated signaling by a moonlighting Gβ protein Asc1/RACK1.PLoS genetics · 2021Article
- Review
- Nuclear Isoforms of Neurofibromin Are Required for Proper Spindle Organization and Chromosome Segregation.Cells · 2020Article
- Biochemical and structural analyses reveal that the tumor suppressor neurofibromin (NF1) forms a high-affinity dimer.The Journal of biological chemistry · 2020Article
- Article
- Ras-Specific GTPase-Activating Proteins-Structures, Mechanisms, and Interactions.Cold Spring Harbor perspectives in medicine · 2019Review
- Ras signaling activates glycosylphosphatidylinositol (GPI) anchor biosynthesis via the GPI-The Journal of biological chemistry · 2018Article
- Ras hyperactivation versus overexpression: Lessons from Ras dynamics in Candida albicans.Scientific reports · 2018Article
- KRH1 and KRH2 are functionally non-redundant in signaling for pseudohyphal differentiation in Saccharomyces cerevisiae.Current genetics · 2017Article
- UBXD Proteins: A Family of Proteins with Diverse Functions in Cancer.International journal of molecular sciences · 2016Review
- Diverse genetic architectures lead to the same cryptic phenotype in a yeast cross.Nature communications · 2016Article
- A plant alkaloid, veratridine, potentiates cancer chemosensitivity by UBXN2A-dependent inhibition of an oncoprotein, mortalin-2.Oncotarget · 2015Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The neurofibromatosis type 1 (NF1) gene encodes the GTPase-activating protein (GAP) neurofibromin, which negatively regulates Ras activity. The yeast Saccharomyces cerevisiae has two neurofibromin homologs, Ira1 and Ira2. To understand how these proteins are regulated, we utilized an unbiased proteomics approach to identify Ira2 and neurofibromin binding partners. We demonstrate that the Gpb1/Krh2 protein binds and negatively regulates Ira2 by promoting its ubiquitin-dependent proteolysis. We extended our findings to show that in mammalian cells, the ETEA/UBXD8 protein directly interacts with and negatively regulates neurofibromin. ETEA contains both UBA and UBX domains. Overexpression of ETEA downregulates neurofibromin in human cells. Purified ETEA, but not a mutant of ETEA that lacks the UBX domain, ubiquitinates the neurofibromin GAP-related domain in vitro. Silencing of ETEA expression increases neurofibromin levels and downregulates Ras activity. These findings provide evidence for conserved ubiquitination pathways regulating the RasGAP proteins Ira2 (in yeast) and neurofibromin (in humans).
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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.