ArticleThe Journal of biological chemistry2012
Cdc6 protein obstructs apoptosome assembly and consequent cell death by forming stable complexes with activated Apaf-1 molecules.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Porcine Beta Defensin 2 Alleviates Apoptosis and Restores Proliferation in IPEC-J2 Cells Challenged with ETEC K88 by Inhibiting the Akt Signaling Pathway.Probiotics and antimicrobial proteins · 2026Article
- A YAP/TAZ-CDC6 Axis Initiates and Maintains Malignant Transformation.Cancer science · 2026Article
- Integrated Bioinformatics Analysis and Experimental Validation of the Role of Cellular Senescence in Osteoporosis.Calcified tissue international · 2025Article
- Comprehensive pan-cancer analysis reveals CDC6 as a potential immunomodulatory agent and promising therapeutic target in pancreatic cancer.Translational cancer research · 2024Article
- CDC6, a key replication licensing factor, is overexpressed and confers poor prognosis in diffuse large B-cell lymphoma.BMC cancer · 2023Article
- Review
- Jasmonates induce Arabidopsis bioactivities selectively inhibiting the growth of breast cancer cells through CDC6 and mTOR.The New phytologist · 2021Article
- Cdc6 as a novel target in cancer: Oncogenic potential, senescence and subcellular localisation.International journal of cancer · 2020Review
- Article
- A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence.BMC genomics · 2018Article
- The Replication Protein Cdc6 Suppresses Centrosome Over-Duplication in a Manner Independent of Its ATPase Activity.Molecules and cells · 2017Article
- Zebrafish cdc6 hypomorphic mutation causes Meier-Gorlin syndrome-like phenotype.Human molecular genetics · 2017Article
- The DNA replication protein Cdc6 inhibits the microtubule-organizing activity of the centrosome.The Journal of biological chemistry · 2017Article
- Transcriptome sequencing combined with bioinformatics predicts potential genes and pathways associated with bupivacaine-induced apoptosis.Animal cells and systems · 2017Article
- General strategy for understanding intracellular molecular interaction cascades that elicit stimulus-invoked biological processes.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2016Article
- A systems biology analysis of apoptosome formation and apoptosis execution supports allosteric procaspase-9 activation.The Journal of biological chemistry · 2014Article
- From computational modelling of the intrinsic apoptosis pathway to a systems-based analysis of chemotherapy resistance: achievements, perspectives and challenges in systems medicine.Cell death & disease · 2014Review
- Mitochondrial regulation of cell death.Cold Spring Harbor perspectives in biology · 2013Review
- Human cytomegalovirus inhibits apoptosis by proteasome-mediated degradation of Bax at endoplasmic reticulum-mitochondrion contacts.Journal of virology · 2013Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cdc6 is the bifunctional AAA+ ATPase that assembles prereplicative complexes on origins of replication and activates p21(CIP1)- or p27(KIP1)-bound Cdk2. During the G(1)-S transition, the Cdc6 gene essential for chromosomal replication is activated by the E2F transcriptional factor. Paradoxically, Apaf-1 encoding the central component of the apoptosome is also activated at the same time and by E2F. Consequently, genes for antipodal life and death are regulated in the same manner by the same transcriptional factor. Here we report a striking solution to this paradox. Besides performing prereplicative complex assembly and Cdk2 activation, Cdc6 obstructed apoptosome assembly by forming stable complexes very likely with a monomer of cytochrome c-activated Apaf-1 molecules. This function depended on its own ATPase domain but not on the cyclin-binding motif. In proliferating rodent fibroblasts, Cdc6 continued to block apoptosome assembly induced by a non-cytochrome c or some other mechanism, suppressing seemingly unintended apoptosis when promoting cell proliferation. Thus, Cdc6 is an AAA+ ATPase with three functions, all working for life.
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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.