ArticleThe Journal of biological chemistry2012
Inhibition of DNA damage-induced apoptosis through Cdc7-mediated stabilization of Tob.
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. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 19 citations in OpenAlex.
- Genetic associations of variants in 10 glaucoma-related genes with POAG risk and structural phenotypes in Korean subjects.Medicine · 2026Article
- Cell cycle exits and U-turns: Quiescence as multiple reversible forms of arrest.Faculty reviews · 2023Review
- Safety, Tolerability, and Pharmacokinetics of TAK-931, a Cell Division Cycle 7 Inhibitor, in Patients with Advanced Solid Tumors: A Phase I First-in-Human Study.Cancer research communications · 2022Article
- MiR-200a with CDC7 as a direct target declines cell viability and promotes cell apoptosis in Wilm's tumor via Wnt/β-catenin signaling pathway.Molecular and cellular biochemistry · 2021Article
- APOBEC3B reporter myeloma cell lines identify DNA damage response pathways leading to APOBEC3B expression.PloS one · 2020Article
- The emerging role for Cullin 4 family of E3 ligases in tumorigenesis.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- DDK dependent regulation of TOP2A at centromeres revealed by a chemical genetics approach.Nucleic acids research · 2016Article
- Acquisition of estrogen independence induces TOB1-related mechanisms supporting breast cancer cell proliferation.Oncogene · 2016Article
- Transducer of ERBB2.1 (TOB1) as a Tumor Suppressor: A Mechanistic Perspective.International journal of molecular sciences · 2015Review
- Structural basis for inhibition of the Tob-CNOT7 interaction by a fragment screening approach.Protein & cell · 2015Article
- Cullin family proteins and tumorigenesis: genetic association and molecular mechanisms.Journal of Cancer · 2015Review
- The stress phenotype makes cancer cells addicted to CDT2, a substrate receptor of the CRL4 ubiquitin ligase.Oncotarget · 2014Article
- Article
- MicroRNA-29a regulates the benzo[a]pyrene dihydrodiol epoxide-induced DNA damage response through Cdc7 kinase in lung cancer cells.Oncogenesis · 2013Article
- Cdc7-dependent and -independent phosphorylation of Claspin in the induction of the DNA replication checkpoint.Cell cycle (Georgetown, Tex.) · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPreventing unnecessary cell death is essential for DNA-damaged cells to carry out the DNA repair process.
resultsCdc7 inhibits the Cul4-DDB1(Cdt2)-dependent Tob degradation.
conclusionCdc7 enables mild DNA-damaged cells to keep their viability by competing with the Tob degradation system. SIGNIFICANCE: Cells deal with moderate DNA damage not only by cessation of the cell cycle but also through direct mediated pro-survival signaling. Cells respond to DNA damage by activating alternate signaling pathways that induce proliferation arrest or apoptosis. The correct balance between these two pathways is important for maintaining genomic integrity and preventing unnecessary cell death. The mechanism by which DNA-damaged cells escape from apoptosis during DNA repair is poorly understood. We show that the DNA replication-initiating kinase Cdc7 actively prevents unnecessary death in DNA-damaged cells. In response to mild DNA damage, Tob levels increase through both a transcriptional mechanism and protein stabilization, resulting in inhibition of pro-apoptotic signaling. Cells lacking Cdc7 expression undergo apoptosis after mild DNA damage, where Cul4-DDB1(Cdt2) induces Tob ubiquitination and subsequent degradation. Cdc7 phosphorylates and interacts with Tob to inhibit the Cul4-DDB1(Cdt2)-dependent Tob degradation. Thus, Cdc7 defines an essential pro-survival signaling pathway by contributing to stabilization of Tob, thereby the viability of DNA-damaged cells being maintained.
Indexed as
Identifiers
What OpenQuestion holds
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.