ArticleThe Journal of biological chemistry2009
Coordinated activation of the origin licensing factor CDC6 and CDK2 in resting human fibroblasts expressing SV40 small T antigen and cyclin E.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Expanding the prostate cancer cell line repertoire with ACRJ-PC28, an AR-negative neuroendocrine cell line derived from an African-Caribbean patient.Cancer research communications · 2022Article
- ADAP restraint of STAT1 signaling regulates macrophage phagocytosis in immune thrombocytopenia.Cellular & molecular immunology · 2022Article
- Review
- Immortalization of human primary prostate epithelial cells via CRISPR inactivation of the CDKN2A locus and expression of telomerase.Prostate cancer and prostatic diseases · 2021Article
- Article
- Preparation for DNA replication: the key to a successful S phase.FEBS letters · 2019Review
- CDK9 inhibition strategy defines distinct sets of target genes.BMC research notes · 2014Article
- CUL4B promotes replication licensing by up-regulating the CDK2-CDC6 cascade.The Journal of cell biology · 2013Article
- Downregulation of Cdc6 and pre-replication complexes in response to methionine stress in breast cancer cells.Cell cycle (Georgetown, Tex.) · 2012Article
- Hypoxic activation of ATR and the suppression of the initiation of DNA replication through cdc6 degradation.Oncogene · 2012Article
- Successive phosphorylation of p27(KIP1) protein at serine-10 and C terminus crucially controls its potency to inactivate Cdk2.The Journal of biological chemistry · 2012Article
- Towards a systems biology approach to mammalian cell cycle: modeling the entrance into S phase of quiescent fibroblasts after serum stimulation.BMC bioinformatics · 2009Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
We have previously shown that SV40 small t antigen (st) cooperates with deregulated cyclin E to activate CDK2 and bypass quiescence in normal human fibroblasts (NHF). Here we show that st expression in serum-starved and density-arrested NHF specifically induces up-regulation and loading of CDC6 onto chromatin. Coexpression of cyclin E results in further accumulation of CDC6 onto chromatin concomitantly with phosphorylation of CDK2 on Thr-160 and CDC6 on Ser-54. Investigation of the mechanism leading to CDC6 accumulation and chromatin loading indicates that st is a potent inducer of cdc6 mRNA expression and increases CDC6 protein stability. We also show that CDC6 expression in quiescent NHF efficiently promotes cyclin E loading onto chromatin, but it is not sufficient to activate CDK2. Moreover, we show that CDC6 expression is linked to phosphorylation of the activating T loop of CDK2 in serum-starved NHF stimulated with mitogens or ectopically expressing cyclin E and st. Our data suggest a model where the combination of st and deregulated cyclin E result in cooperative and coordinated activation of both an essential origin licensing factor, CDC6, and an activity required for origin firing, CDK2, resulting in progression from quiescence to S phase.
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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.