ArticleOncogene1999
TC21 and Ras share indistinguishable transforming and differentiating activities.
Article in Oncogene, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
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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.
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Who cites it
32 citing papers in PubMed, 73 citations in OpenAlex.
- Active R-RAS2/TC21 prevents cell cycle arrest and morphological alterations in mouse embryonic fibroblasts lacking RAS proteins.Oncogene · 2025Article
- In Silico Born Designed Anti-EGFR Aptamer Gol1 Has Anti-Proliferative Potential for Patient Glioblastoma Cells.International journal of molecular sciences · 2025Article
- Longitudinal plasma proteome profiling reveals the diversity of biomarkers for diagnosis and cetuximab therapy response of colorectal cancer.Nature communications · 2024Article
- Mice Overexpressing Wild-TypeCancers · 2023Article
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- Overexpression of wild type RRAS2, without oncogenic mutations, drives chronic lymphocytic leukemia.Molecular cancer · 2022Article
- R-Ras subfamily proteins elicit distinct physiologic effects and phosphoproteome alterations in neurofibromin-null MPNST cells.Cell communication and signaling : CCS · 2021Article
- The Role of R-Ras Proteins in Normal and Pathologic Migration and Morphologic Change.The American journal of pathology · 2021Review
- Activating Mutations of RRAS2 Are a Rare Cause of Noonan Syndrome.American journal of human genetics · 2019Article
- Concepts and advances in cancer therapeutic vulnerabilities in RAS membrane targeting.Seminars in cancer biology · 2019Review
- R-Ras1 and R-Ras2 Are Essential for Oligodendrocyte Differentiation and Survival for Correct Myelination in the Central Nervous System.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
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- ERK1/2-induced phosphorylation of R-Ras GTPases stimulates their oncogenic potential.Oncogene · 2016Article
- The genomic landscape of juvenile myelomonocytic leukemia.Nature genetics · 2015Article
- R-RAS2 overexpression in tumors of the human central nervous system.Molecular cancer · 2013Article
- The Expression, Purification, and Characterization of a Ras Oncogene (Bras2) in Silkworm (Bombyx mori).International journal of genomics · 2013Article
- In vivo regulation of TGF-β by R-Ras2 revealed through loss of the RasGAP protein NF1.Cancer research · 2012Article
- siRNA-mediated downregulation of TC21 sensitizes esophageal cancer cells to cisplatin.World journal of gastroenterology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Constitutively activated mutants of the Ras-related protein TC21/R-Ras2 cause tumorigenic transformation of NIH3T3 cells. However, unlike Ras, TC21 fails to bind to and activate the Raf-1 serine-threonine kinase. Thus, whereas Ras transformation is critically dependent on Raf-1 TC21 activity is promoted by activation of Raf-independent signaling pathways. In the present study, we have further compared the functions of Ras and TC21. First we determined the basis for the inability of TC21 to activate Raf-1. Whereas Ras can interact with the two distinct Ras-binding sequences in NH2-terminus of Raf-1, designated RBS1 and Raf-Cys, TC21 could only bind Raf-Cys. Thus, the inability of TC21 to bind to RBS1 may prevent it from promoting the translocation of Raf-1 to the plasma membrane. Second, we found that TC21 is an activator of the JNK and p38, but not ERK, mitogen-activated protein kinase cascades and that TC21 transforming activity was dependent on Rac function. Thus, like Ras, TC21 may activate a Rac/JNK pathway. Third, we determined if TC21 could cause the same biological consequences as Ras in three distinct cell types. Like Ras, activated TC21 caused transformation of RIE-1 rat intestinal epithelial cells and terminal differentiation of PC12 pheochromocytoma cells. Finally, activated TC21 blocked serum starvation-induced differentiation of C2 myoblasts, whereas dominant negative TC21 greatly accelerated this differentiation process. Therefore, TC21 and Ras share indistinguishable biological activities in all cell types that we have evaluated. These results support the importance of Raf-independent pathways in mediating the actions of Ras and TC21.
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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.