ArticleMolecular and cellular biology1997
WAF1 retards S-phase progression primarily by inhibition of cyclin-dependent kinases.
Article in Molecular and cellular biology, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed.
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- Inhibition of the ATR kinase enhances 5-FU sensitivity independently of nonhomologous end-joining and homologous recombination repair pathways.The Journal of biological chemistry · 2020Article
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- Aurantoside C Targets and Induces Apoptosis in Triple Negative Breast Cancer Cells.Marine drugs · 2018Article
- Synchronous and Time-Dependent Expression of Cyclins, Cyclin-Dependant Kinases, and Apoptotic Genes in the Rumen Epithelia of Butyrate-Infused Goats.Frontiers in physiology · 2018Article
- PEPD is a pivotal regulator of p53 tumor suppressor.Nature communications · 2017Article
- Overexpression of non‑SMC condensin I complex subunit G serves as a promising prognostic marker and therapeutic target for hepatocellular carcinoma.International journal of molecular medicine · 2017Article
- Synergistic anti-tumor effect of bullfrog sialic acid-binding lectin and pemetrexed in malignant mesothelioma.Oncotarget · 2017Article
- p53 overexpression increases chemosensitivity in multidrug-resistant osteosarcoma cell lines.Cancer chemotherapy and pharmacology · 2016Article
- Tissue Inhibitor of Matrix Metalloproteinases-1 Knockdown Suppresses the Proliferation of Human Adipose-Derived Stem Cells.Stem cells international · 2016Article
- Article
- Synergistic suppression of human breast cancer cells by combination of plumbagin and zoledronic acid In vitro.Acta pharmacologica Sinica · 2015Article
- The T-Box factor TBX3 is important in S-phase and is regulated by c-Myc and cyclin A-CDK2.Cell cycle (Georgetown, Tex.) · 2015Article
16 more citing papers are in PubMed but not listed here.
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3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p21(WAF1/CIP1/sdi1) gene product (WAF1) inhibits DNA replication in vitro (J. Chen, P. Jackson, M. Kirschner, and A. Dutta, Nature 374:386-388, 1995; S. Waga, G. Hannon, D. Beach, and B. Stillman, Nature 369:574-578, 1994), but in vivo studies on the antiproliferative activity of WAF1 have not resolved G1-phase arrest from potential inhibition of S-phase progression. Here, we demonstrate that elevated WAF1 expression can retard replicative DNA synthesis in vivo. The WAF1-mediated inhibitory effect could be antagonized by cyclin A, cyclin E, or the simian virus 40 small-t antigen with no decrease in the levels of WAF1 protein in transfected cells. Proliferating-cell nuclear antigen (PCNA) overexpression was neither necessary nor sufficient to antagonize WAF1 action. Expression of the N-terminal domain of WAF1, responsible for cyclin-dependent kinase (CDK) interaction, had the same effect as full-length WAF1, while the PCNA binding C terminus exhibited modest activity. We conclude that S-phase progression in mammalian cells is dependent on continuing cyclin and CDK activity and that WAF1 affects S phase primarily through cyclin- and CDK-dependent pathways.
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