ArticleOncogene2000
Disruption of TGF-beta growth inhibition by oncogenic ras is linked to p27Kip1 mislocalization.
Article in Oncogene, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 57 citations in OpenAlex.
- Hallmarks of cancer and hallmarks of aging.Aging · 2022Article
- The Multifaceted p21 (Cip1/Waf1/Cancers · 2019Review
- Loss of p27Kip¹ promotes metaplasia in the pancreas via the regulation of Sox9 expression.Oncotarget · 2015Article
- KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition.British journal of cancer · 2014Article
- Antibody-directed coupling of endoglin and MMP-14 is a key mechanism for endoglin shedding and deregulation of TGF-β signaling.Oncogene · 2014Article
- Clinical significance of cell cycle inhibitors in hepatocellular carcinoma.Medical molecular morphology · 2013Review
- Dual effects of Ral-activated pathways on p27 localization and TGF-β signaling.Molecular biology of the cell · 2013Article
- Coated pit-mediated endocytosis of the type I transforming growth factor-β (TGF-β) receptor depends on a di-leucine family signal and is not required for signaling.The Journal of biological chemistry · 2012Article
- Low molecular weight cyclin E is associated with p27-resistant, high-grade, high-stage and invasive bladder cancer.Cell cycle (Georgetown, Tex.) · 2012Article
- An integrated view of cyclin E function and regulation.Cell cycle (Georgetown, Tex.) · 2012Article
- Multiple degradation pathways regulate versatile CIP/KIP CDK inhibitors.Trends in cell biology · 2012Review
- Article
- p27: a barometer of signaling deregulation and potential predictor of response to targeted therapies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2011Review
- CRL2(LRR-1) targets a CDK inhibitor for cell cycle control in C. elegans and actin-based motility regulation in human cells.Developmental cell · 2010Article
- RSK1 drives p27Kip1 phosphorylation at T198 to promote RhoA inhibition and increase cell motility.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Different domains regulate homomeric and heteromeric complex formation among type I and type II transforming growth factor-beta receptors.The Journal of biological chemistry · 2009Article
- Discovery of an oncogenic activity in p27Kip1 that causes stem cell expansion and a multiple tumor phenotype.Genes & development · 2007Article
- Molecular control of nuclear and subnuclear targeting of the plant CDK inhibitor ICK1 and ICK1-mediated nuclear transport of CDKA.Plant molecular biology · 2006Article
- A pathway in quiescent cells that controls p27Kip1 stability, subcellular localization, and tumor suppression.Genes & development · 2006Article
- Pathway- and expression level-dependent effects of oncogenic N-Ras: p27(Kip1) mislocalization by the Ral-GEF pathway and Erk-mediated interference with Smad signaling.Molecular and cellular biology · 2005Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expression of oncogenic Ras in epithelial tumor cells is linked to the loss of transforming growth factor-beta (TGF-beta) anti-proliferative activity, and was proposed to involve inhibition of Smad2/3 nuclear translocation. Here we studied several epithelial cell lines expressing oncogenic N-RasK61 and show that TGF-beta-induced nuclear translocation of and transcriptional activation by Smad2/3 were unaffected. In contrast, oncogenic Ras mediated nuclearto-cytoplasmic mislocalization of p27KiP1 (p27) and of the cyclin-dependent kinase (CDK) CDK6, but not CDK2. Concomitantly, oncogenic Ras abrogated the ability of TGF-beta to release p27 from CDK6, to enhance its binding to CDK2 and to inhibit CDK2 activity. Inactivation of Ras by a specific antagonist restored the growth inhibitory response to TGF-beta with concurrent normalization of p27 and CDK6 localization. Therefore, the disruption of TGF-beta-mediated growth inhibition by oncogenic Ras appears to be due to lack of inhibition of CDK2, caused by the sequestration of p27 and CDK2 in different subcellular compartments and by the loss of TGF-beta-induced partner switching of p27 from CDK6 to CDK2.
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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.