ArticleThe Journal of biological chemistry2008
Cyclin E and SV40 small T antigen cooperate to bypass quiescence and contribute to transformation by activating CDK2 in human fibroblasts.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Mechanisms of Viral Oncogenesis: DNA and RNA Viruses in Human Cancer.Journal of inflammation research · 2025Review
- Review
- Association Between Simian Virus 40 and Human Tumors.Frontiers in oncology · 2019Review
- Human Polyomaviruses: The Battle of Large and Small Tumor Antigens.Virology : research and treatment · 2017Review
- Possible pharmacotherapy for nifedipine-induced gingival overgrowth: 18α-glycyrrhetinic acid inhibits human gingival fibroblast growth.British journal of pharmacology · 2016Article
- CDK9 inhibition strategy defines distinct sets of target genes.BMC research notes · 2014Article
- A chrysin derivative suppresses skin cancer growth by inhibiting cyclin-dependent kinases.The Journal of biological chemistry · 2013Article
- Complex effects of flavopiridol on the expression of primary response genes.Cell division · 2012Article
- Human gene control by vital oncogenes: revisiting a theoretical model and its implications for targeted cancer therapy.International journal of molecular sciences · 2012Review
- Human Merkel cell polyomavirus small T antigen is an oncoprotein targeting the 4E-BP1 translation regulator.The Journal of clinical investigation · 2011Article
- B55alpha PP2A holoenzymes modulate the phosphorylation status of the retinoblastoma-related protein p107 and its activation.The Journal of biological chemistry · 2010Article
- Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens.Seminars in cancer biology · 2009Review
- Coordinated activation of the origin licensing factor CDC6 and CDK2 in resting human fibroblasts expressing SV40 small T antigen and cyclin E.The Journal of biological chemistry · 2009Article
- Cyclin-dependent kinase 3-mediated activating transcription factor 1 phosphorylation enhances cell transformation.Cancer research · 2008Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cyclin E overexpression is observed in multiple human tumors and linked to poor prognosis. We have previously shown that ectopic expression of cyclin E is sufficient to induce mitogen-independent cell cycle entry in a variety of tumor/immortal cell lines. Here we have investigated the rate-limiting step leading to cell cycle entry in quiescent normal human fibroblasts (NHF) ectopically expressing cyclin E. We found that in serum-starved NHF, cyclin E forms inactive complexes with CDK2 and fails to induce DNA synthesis. Coexpression of SV40 small t antigen (st), but not other tested oncogenes, efficiently induces mitogen-independent CDK2 phosphorylation on Thr-160, CDK2 activation, and DNA synthesis. Additionally, in contact-inhibited NHF ectopically expressing cyclin E, st induces cell cycle entry, continued proliferation, and foci formation. Coexpression of cyclin E and st also bypasses G(0)/G(1) arrests induced by CDK inhibitors. Although CDK2 is dispensable for G(0)/G(1) cell cycle entry and normal proliferation in mammals, CDK2 activity is an essential rate-limiting step in NHF with deregulated cyclin E expression and altered PP2A activity, which endows primary cells with transformed features. Consequently, CDK2 could be targeted therapeutically in tumors that involve these alterations. These data also suggest that alterations prior to cyclin E deregulation facilitate proliferation of tumor cells by bypassing mitogenic requirements and negative regulation by adjacent cells.
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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.