ArticleMolecular biology of the cell2005
Developmental activation of the Rb-E2F pathway and establishment of cell cycle-regulated cyclin-dependent kinase activity during embryonic stem cell differentiation.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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92 citing papers in PubMed, 167 citations in OpenAlex.
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- Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy.Stem cell reports · 2025Review
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- Targeting Cell Cycle Facilitates E1A-Independent Adenoviral Replication.Journal of virology · 2023Article
- G1/S restriction point coordinates phasic gene expression and cell differentiation.Nature communications · 2022Article
- Atypical cyclin P regulates cancer cell stemness through activation of the WNT pathway.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Age-related neurodegeneration and cognitive impairments of NRMT1 knockout mice are preceded by misregulation of RB and abnormal neural stem cell development.Cell death & disease · 2021Article
- Transcription Landscape of the Early Developmental Biology in Pigs.Animals : an open access journal from MDPI · 2021Article
- G1-phase progression in pluripotent stem cells.Cellular and molecular life sciences : CMLS · 2021Review
- Mutation of SPINOPHILIN (PPP1R9B) found in human tumors promotes the tumorigenic and stemness properties of cells.Theranostics · 2021Article
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- Role of cyclins and cyclin-dependent kinases in pluripotent stem cells and their potential as a therapeutic target.Seminars in cell & developmental biology · 2020Review
- Cdk1 Controls Global Epigenetic Landscape in Embryonic Stem Cells.Molecular cell · 2020Article
32 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To understand cell cycle control mechanisms in early development and how they change during differentiation, we used embryonic stem cells to model embryonic events. Our results demonstrate that as pluripotent cells differentiate, the length of G(1) phase increases substantially. At the molecular level, this is associated with a significant change in the size of active cyclin-dependent kinase (Cdk) complexes, the establishment of cell cycle-regulated Cdk2 activity and the activation of a functional Rb-E2F pathway. The switch from constitutive to cell cycle-dependent Cdk2 activity coincides with temporal changes in cyclin A2 and E1 protein levels during the cell cycle. Transcriptional mechanisms underpin the down-regulation of cyclin levels and the establishment of their periodicity during differentiation. As pluripotent cells differentiate and pRb/p107 kinase activities become cell cycle dependent, the E2F-pRb pathway is activated and imposes cell cycle-regulated transcriptional control on E2F target genes, such as cyclin E1. These results suggest the existence of a feedback loop where Cdk2 controls its own activity through regulation of cyclin E1 transcription. Changes in rates of cell division, cell cycle structure and the establishment of cell cycle-regulated Cdk2 activity can therefore be explained by activation of the E2F-pRb pathway.
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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.