Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/27486
Citations | ||
Scopus | Web of Science® | Altmetric |
---|---|---|
?
|
?
|
Type: | Journal article |
Title: | Developmental activation of the Rb-E2F pathway and establishment of cell cycle-regulated cyclin-dependent kinase activity during embryonic stem cell differentiation |
Author: | White, J. Stead, E. Faast, R. Conn, S. Cartwright, P. Dalton, S. |
Citation: | Molecular Biology of the Cell, 2005; 16(4):2018-2027 |
Publisher: | Amer Soc Cell Biology |
Issue Date: | 2005 |
ISSN: | 1059-1524 1939-4586 |
Statement of Responsibility: | Josephine White, Elaine Stead, Renate Faast, Simon Conn, Peter Cartwright, and Stephen Dalton |
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 G₁ 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. |
Keywords: | Cells, Cultured Stem Cells Animals Mice Cyclin-Dependent Kinases Cyclin E Cell Cycle Proteins DNA-Binding Proteins Retinoblastoma Protein Transcription Factors RNA, Messenger Cell Cycle Cell Differentiation Transcription, Genetic Down-Regulation E2F Transcription Factors Embryo, Mammalian Promoter Regions, Genetic |
DOI: | 10.1091/mbc.E04-12-1056 |
Published version: | http://dx.doi.org/10.1091/mbc.e04-12-1056 |
Appears in Collections: | Aurora harvest 2 Molecular and Biomedical Science publications |
Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.