ArticleOncogene2000
A dominant negative RAS-specific guanine nucleotide exchange factor reverses neoplastic phenotype in K-ras transformed mouse fibroblasts.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- A Focused Review of Ras Guanine Nucleotide-Releasing Protein 1 in Immune Cells and Cancer.International journal of molecular sciences · 2023Review
- Suppression of the HBP Function Increases Pancreatic Cancer Cell Sensitivity to a Pan-RAS Inhibitor.Cells · 2021Article
- Pancreatic Tumorigenesis: Oncogenic KRAS and the Vulnerability of the Pancreas to Obesity.Cancers · 2021Review
- Article
- Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis.PLoS genetics · 2016Article
- The Significance of Ras Activity in Pancreatic Cancer Initiation.International journal of biological sciences · 2016Review
- Glucose starvation induces cell death in K-ras-transformed cells by interfering with the hexosamine biosynthesis pathway and activating the unfolded protein response.Cell death & disease · 2013Article
- A Rab11a-Rab8a-Myo5B network promotes stretch-regulated exocytosis in bladder umbrella cells.Molecular biology of the cell · 2013Article
- Article
- Mapping cancer cell metabolism with(13)C flux analysis: Recent progress and future challenges.Journal of carcinogenesis · 2013Article
- Cancer cell growth and survival as a system-level property sustained by enhanced glycolysis and mitochondrial metabolic remodeling.Frontiers in physiology · 2012Article
- Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth.Molecular systems biology · 2011Article
- Requirement of the NF-kappaB subunit p65/RelA for K-Ras-induced lung tumorigenesis.Cancer research · 2010Article
- Glutamine deprivation induces abortive s-phase rescued by deoxyribonucleotides in k-ras transformed fibroblasts.PloS one · 2009Article
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Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ras proteins are small GTPases playing a pivotal role in cell proliferation and differentiation. Their activation state depends on the competing action of GTPase Activating Proteins (GAP) and Guanine nucleotide Exchange Factors (GEF). A tryptophan residue (Trp1056 in CDC25Mm-GEF), conserved in all ras-specific GEFs identified so far has been previously shown to be essential for GEF activity. Its substitution with glutamic acid results in a catalytically inactive mutant, which is able to efficiently displace wild-type GEF from p21ras and to originate a stable ras/GEF binary complex due to the reduced affinity of the nucleotide-free ras/GEF complex for the incoming nucleotide. We show here that this 'ras-sequestering property' can be utilized to attenuate ras signal transduction pathways in mouse fibroblasts transformed by oncogenic ras. In fact overexpression of the dominant negative GEFW1056E in stable transfected cells strongly reduces intracellular ras-GTP levels in k-ras transformed fibroblasts. Accordingly, the transfected fibroblasts revert to wild-type phenotype on the basis of morphology, cell cycle and anchorage independent growth. The reversion of the transformed phenotype is accompanied by DNA endoreduplication. The possible use of dominant negative ras-specific GEFs as a tool to down-regulate tumor growth is discussed.
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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.