ArticleMolecular and cellular biology2001
Retinoblastoma tumor suppressor protein signals through inhibition of cyclin-dependent kinase 2 activity to disrupt PCNA function in S phase.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Analysing Differential Alternative Splicing Events and Their Impact on Retinoblastoma Progression Using RNA-seq Metadata.Asian Pacific journal of cancer prevention : APJCP · 2025Pooled it
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- Downregulation of FTL decreases proliferation of malignant mesothelioma cells by inducing GOncology letters · 2022Article
- Pharmacological Inhibition of Cyclin-Dependent Kinases Triggers Anti-Fibrotic Effects in Hepatic Stellate Cells In Vitro.International journal of molecular sciences · 2020Article
- The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer.International journal of molecular sciences · 2020Review
- Poly (ADP) Ribose Glycohydrolase Can Be Effectively Targeted in Pancreatic Cancer.Cancer research · 2019Article
- Targeting cyclin-dependent kinases for the treatment of pulmonary arterial hypertension.Nature communications · 2019Article
- Posttranscriptional Regulation ofCancer research · 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
- Bicyclol induces cell cycle arrest and autophagy in HepG2 human hepatocellular carcinoma cells through the PI3K/AKT and Ras/Raf/MEK/ERK pathways.BMC cancer · 2016Article
- Dual CCNE1/PIK3CA targeting is synergistic in CCNE1-amplified/PIK3CA-mutated uterine serous carcinomas in vitro and in vivo.British journal of cancer · 2016Article
- The history and future of targeting cyclin-dependent kinases in cancer therapy.Nature reviews. Drug discovery · 2015Review
- Dual roles of PARP-1 promote cancer growth and progression.Cancer discovery · 2012Article
- Article
- The retinoblastoma family of proteins and their regulatory functions in the mammalian cell division cycle.Cell division · 2012Article
- Cyclin-dependent kinase 4/6 activity is a critical determinant of pre-replication complex assembly.Oncogene · 2008Article
- NFATc1 targets cyclin A in the regulation of vascular smooth muscle cell multiplication during restenosis.The Journal of biological chemistry · 2008Article
- 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.Molecular and cellular biology · 2006Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The retinoblastoma tumor suppressor protein (RB) is a negative regulator of the cell cycle that inhibits both G(1) and S-phase progression. While RB-mediated G(1) inhibition has been extensively studied, the mechanism utilized for S-phase inhibition is unknown. To delineate the mechanism through which RB inhibits DNA replication, we generated cells which inducibly express a constitutively active allele of RB (PSM-RB). We show that RB-mediated S-phase inhibition does not inhibit the chromatin binding function of MCM2 or RPA, suggesting that RB does not regulate the prereplication complex or disrupt early initiation events. However, activation of RB in S-phase cells disrupts the chromatin tethering of PCNA, a requisite component of the DNA replication machinery. The action of RB was S phase specific and did not inhibit the DNA damage-mediated association of PCNA with chromatin. We also show that RB-mediated PCNA inhibition was dependent on downregulation of CDK2 activity, which was achieved through the downregulation of cyclin A. Importantly, restoration of cyclin-dependent kinase 2 (CDK2)-cyclin A and thus PCNA activity partially restored S-phase progression in the presence of active RB. Therefore, the data presented identify RB-mediated regulation of PCNA activity via CDK2 attenuation as a mechanism through which RB regulates S-phase progression. Together, these findings identify a novel pathway of RB-mediated replication inhibition.
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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.