ArticleThe EMBO journal1998
A novel function of adenovirus E1A is required to overcome growth arrest by the CDK2 inhibitor p27(Kip1).
Article in The EMBO journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 53 citations in OpenAlex.
- Distinct Regulation of theCells · 2026Article
- DEAD/H Box 5 (DDX5) Augments E2F1-Induced Cell Death Independent of the Tumor Suppressor p53.International journal of molecular sciences · 2024Article
- Emerging antiviral therapeutics for human adenovirus infection: Recent developments and novel strategies.Antiviral research · 2021Review
- Hypoxia inhibits mesenchymal stem cell proliferation through HIF1α-dependent regulation of P27.Molecular and cellular biochemistry · 2016Article
- New roles for cyclin-dependent kinases in T cell biology: linking cell division and differentiation.Nature reviews. Immunology · 2014Review
- Functional ablation of pRb activates Cdk2 and causes antiestrogen resistance in human breast cancer cells.PloS one · 2007Article
- Identification of novel E2F1 target genes regulated in cell cycle-dependent and independent manners.Oncogene · 2006Article
- Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus.Oncogene · 2005Review
- A cancer-specific transcriptional signature in human neoplasia.The Journal of clinical investigation · 2005Article
- Anoxic fibroblasts activate a replication checkpoint that is bypassed by E1a.Molecular and cellular biology · 2003Article
- Cyclins E1 and E2 are required for endoreplication in placental trophoblast giant cells.The EMBO journal · 2003Article
- Pharmacological cyclin-dependent kinase inhibitors inhibit replication of wild-type and drug-resistant strains of herpes simplex virus and human immunodeficiency virus type 1 by targeting cellular, not viral, proteins.Journal of virology · 2002Article
- Loss of p27(Kip1) but not p21(Cip1) decreases survival and synergizes with MYC in murine lymphomagenesis.The EMBO journal · 2002Article
- Np95 is regulated by E1A during mitotic reactivation of terminally differentiated cells and is essential for S phase entry.The Journal of cell biology · 2002Article
- Adenoviruses with Tcf binding sites in multiple early promoters show enhanced selectivity for tumour cells with constitutive activation of the wnt signalling pathway.Gene therapy · 2002Article
- Article
- E1A modulates phosphorylation of p130 and p107 by differentially regulating the activity of G1/S cyclin/CDK complexes.Oncogene · 2001Article
- Biology of human papillomaviruses.International journal of experimental pathology · 2001Review
- Inhibition of S-phase progression by adeno-associated virus Rep78 protein is mediated by hypophosphorylated pRb.The EMBO journal · 2000Article
- Density-dependent growth inhibition of fibroblasts ectopically expressing p27(kip1).Molecular biology of the cell · 2000Article
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We show here that the adenovirus E1A oncoprotein prevents growth arrest by the CDK2 inhibitor p27(Kip1) (p27) in rodent fibroblasts. However, E1A neither binds p27 nor prevents inhibition of CDK2 complexes in vivo. In contrast, the amount of free p27 available to inhibit cyclin E/CDK2 is increased in E1A-expressing cells, owing to reduced expression of cyclins D1 and D3. Moreover, E1A allows cell proliferation in the presence of supraphysiological p27 levels, while c-Myc, known to induce a cellular p27-inhibitory activity, is only effective against physiological p27 concentrations. E1A also bypasses G1 arrest by roscovitine, a chemical inhibitor of CDK2. Altogether, these findings imply that E1A can act downstream of p27 and CDK2. Retinoblastoma (pRb)-family proteins are known CDK substrates; as expected, association of E1A with these proteins (but not with p300/CBP) is required for E1A to prevent growth arrest by either p27 or the CDK4/6 inhibitor p16(INK4a). Bypassing CDK2 inhibition requires an additional function of E1A: the mutant E1A Delta26-35 does not overcome p27-induced arrest, while it binds pRb-family proteins, prevents p16-induced arrest, and alleviates pRb-mediated repression of E2F-1 transcriptional activity (although E1A Delta26-35 fails to restore expression of E2F-regulated genes in p27-arrested cells). We propose that besides the pRb family, E1A targets specific effector(s) of CDK2 in G1-S control.
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