ArticleMolecular and cellular biology2006
Distinct action of the retinoblastoma pathway on the DNA replication machinery defines specific roles for cyclin-dependent kinase complexes in prereplication complex assembly and S-phase progression.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 24 papers.
What it found
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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.
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
24 citing papers in PubMed, 34 citations in OpenAlex.
- Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review.Molecular diagnosis & therapy · 2024Review
- Key Proteins of Replication Stress Response and Cell Cycle Control as Cancer Therapy Targets.International journal of molecular sciences · 2024Review
- Retraction Note: Cyclin-dependent kinase 4/6 activity is a critical determinant of pre-replication complex assembly.Oncogene · 2023Article
- Article
- Targeting the Vulnerability of RB Tumor Suppressor Loss in Triple-Negative Breast Cancer.Cell reports · 2018Article
- Disruption of CDK-resistant chromatin association by pRB causes DNA damage, mitotic errors, and reduces Condensin II recruitment.Cell cycle (Georgetown, Tex.) · 2017Article
- MMSET is dynamically regulated during cell-cycle progression and promotes normal DNA replication.Cell cycle (Georgetown, Tex.) · 2016Article
- Potentiation of Carboplatin-Mediated DNA Damage by the Mdm2 Modulator Nutlin-3a in a Humanized Orthotopic Breast-to-Lung Metastatic Model.Molecular cancer therapeutics · 2015Article
- Article
- KMTase Set7/9 is a critical regulator of E2F1 activity upon genotoxic stress.Cell death and differentiation · 2014Article
- Oncogenic protein MTBP interacts with MYC to promote tumorigenesis.Cancer research · 2014Article
- The Mcm2-7 replicative helicase: a promising chemotherapeutic target.BioMed research international · 2014Review
- RB deletion disrupts coordination between DNA replication licensing and mitotic entry in vivo.Molecular biology of the cell · 2011Article
- The relative contributions of the p53 and pRb pathways in oncogene-induced melanocyte senescence.Aging · 2009Article
- Prohibitin physically interacts with MCM proteins and inhibits mammalian DNA replication.Cell cycle (Georgetown, Tex.) · 2009Article
- Identification and functional analysis of a novel cyclin e/cdk2 substrate ankrd17.The Journal of biological chemistry · 2009Article
- Activation of the retinoblastoma tumor suppressor mediates cell cycle inhibition and cell death in specific cervical cancer cell lines.Molecular carcinogenesis · 2009Article
- Analysis of re-replication from deregulated origin licensing by DNA fiber spreading.Nucleic acids research · 2009Article
- Article
- Cyclin-dependent kinase 4/6 activity is a critical determinant of pre-replication complex assembly.Oncogene · 2008Article
Corrections and comments
- Retraction · 2020-08-14Duplication of/in Image · Manipulation of Images ·
- Retracted
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The retinoblastoma (RB) and p16ink4a tumor suppressors are believed to function in a linear pathway that is functionally inactivated in a large fraction of human cancers. Recent studies have shown that RB plays a critical role in regulating S phase as a means for suppressing aberrant proliferation and controlling genome stability. Here, we demonstrate a novel role for p16ink4a in replication control that is distinct from that of RB. Specifically, p16ink4a disrupts prereplication complex assembly by inhibiting mini-chromosome maintenance (MCM) protein loading in G1, while RB was found to disrupt replication in S phase through attenuation of PCNA function. This influence of p16ink4a on the prereplication complex was dependent on the presence of RB and the downregulation of cyclin-dependent kinase (CDK) activity. Strikingly, the inhibition of CDK2 activity was not sufficient to prevent the loading of MCM proteins onto chromatin, which supports a model wherein the composite action of multiple G1 CDK complexes regulates prereplication complex assembly. Additionally, p16ink4a attenuated the levels of the assembly factors Cdt1 and Cdc6. The enforced expression of these two licensing factors was sufficient to restore the assembly of the prereplication complex yet failed to promote S-phase progression due to the continued absence of PCNA function. Combined, these data reveal that RB and p16ink4a function through distinct pathways to inhibit the replication machinery and provide evidence that stepwise regulation of CDK activity interfaces with the replication machinery at two discrete execution points.
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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.