Induction of DNA replication in adult rat neurons by deregulation of the retinoblastoma/E2F G1 cell cycle pathway. Cell Growth Differ 2000 Dec;11(12):625-33
Date
01/10/2001Pubmed ID
11149597Scopus ID
2-s2.0-0034524238 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
In adult organisms, a range of proliferative capacities are exhibited by different cell types. Stem cell populations in many tissues readily enter the cell cycle when presented with serum growth factors or other proliferative cues, whereas "terminally" postmitotic cells, such as cardiac myocytes and neurons, fail to do so. Although they rarely show evidence of a proliferative capacity in vivo, there is accumulating evidence to suggest that DNA synthesis can be triggered in postmitotic cells. We now show that cultured adult rat sensory neurons can replicate DNA in response to ectopic expression of E2F1 or E2F2 and that this is augmented by expression of cyclin-dependent kinase activities. We also find that addition of serum and laminin inhibits the E2F-induced S-phase in neurons but not in nonneuronal cells in the same cultures. We conclude that, although terminally differentiated neurons possess the capacity to reinitiate DNA replication in response to G1 regulatory activities, they fail to do so in the presence of signals that do not inhibit S-phase in other cell types in the same cultures. This suggests the existence of cell type-specific inhibitory pathways induced by these signals.
Author List
Smith DS, Leone G, DeGregori J, Ahmed MN, Qumsiyeh MB, Nevins JRAuthor
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdenoviridaeAdenovirus E2 Proteins
Animals
Blotting, Western
Bromodeoxyuridine
Carrier Proteins
Cell Cycle
Cell Cycle Proteins
Cell Differentiation
Cells, Cultured
DNA
DNA-Binding Proteins
E2F Transcription Factors
E2F1 Transcription Factor
E2F2 Transcription Factor
G1 Phase
Ganglia, Spinal
In Situ Hybridization, Fluorescence
Laminin
Neurons
Rats
Retinoblastoma Protein
Retinoblastoma-Binding Protein 1
Time Factors
Transcription Factor DP1
Transcription Factors
