ArticleThe Journal of cell biology2006
Cleavage of Cdc6 by caspase-3 promotes ATM/ATR kinase-mediated apoptosis of HeLa cells.
Article in The Journal of cell biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 33 citations in OpenAlex.
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- ORChestra coordinates the replication and repair music.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Article
- Caspase-3 knockout attenuates radiation-induced tumor repopulation via impairing the ATM/p53/Cox-2/PGEAging · 2020Article
- Article
- Cell-Cycle Cross Talk with Caspases and Their Substrates.Cold Spring Harbor perspectives in biology · 2020Review
- Antagonizing CDK8 Sensitizes Colorectal Cancer to Radiation Through Potentiating the Transcription of e2f1 Target Gene apaf1.Frontiers in cell and developmental biology · 2020Article
- Article
- The nuclear γ-H2AX apoptotic ring: implications for cancers and autoimmune diseases.Cellular and molecular life sciences : CMLS · 2014Review
- Quantitative proteomics of Xenopus laevis embryos: expression kinetics of nearly 4000 proteins during early development.Scientific reports · 2014Article
- Tissue-spanning redox gradient-dependent assembly of native human papillomavirus type 16 virions.Journal of virology · 2009Article
- Polo-like kinase 1 depletion induces DNA damage in early S prior to caspase activation.Molecular and cellular biology · 2009Article
- Generation of an indestructible cyclin B1 by caspase-6-dependent cleavage during mitotic catastrophe.Oncogene · 2009Article
- Mechanisms to control rereplication and implications for cancer.Current opinion in cell biology · 2007Review
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
We show that caspase-3 cleaves Cdc6 at D(290)/S and D(442)/G sites, producing p32-tCdc6 (truncated Cdc6) and p49-tCdc6, respectively, during etoposide- or tumor necrosis factor (TNF)-alpha-induced apoptosis. The expression of these tCdc6 proteins, p32- and p49-tCdc6, promotes etoposide-induced apoptosis. The expression of tCdc6 perturbs the loading of Mcm2 but not Orc2 onto chromatin and activates ataxia telangiectasia mutated (ATM) and ATM and Rad-3 related (ATR) kinase activities with kinetics similar to that of the phosphorylation of Chk1/2. The activation kinetics are consistent with elevated cellular levels of p53 and mitochondrial levels of Bax. The tCdc6-induced effects are all suppressed to control levels by expressing a Cdc6 mutant that cannot be cleaved by caspase-3 (Cdc6-UM). Cdc6-UM expression attenuates the TNF-alpha-induced activation of ATM and caspase-3 activities. When ATM or ATR is down-expressed by using the small interfering RNA technique, the TNF-alpha- or tCdc6-induced activation of caspase-3 activities is suppressed in the cells. These results suggest that tCdc6 proteins act as dominant-negative inhibitors of replication initiation and that they disrupt chromatin structure and/or induce DNA damage, leading to the activation of ATM/ATR kinase activation and p53-Bax-mediated apoptosis.
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Registered trials
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