Sang, Liyun and Coller, Hilary A and Roberts, James M (2008) Control of the reversibility of cellular quiescence by the transcriptional repressor HES1. Science (New York, N.Y.), 321 (5892). pp. 1095-1100. ISSN 1095-9203
Abstract
The mechanisms by which quiescent cells, including adult stem cells, preserve their ability to resume proliferation after weeks or even years of cell cycle arrest are not known. We report that reversibility is not a passive property of nondividing cells, because enforced cell cycle arrest for a period as brief as 4 days initiates spontaneous, premature, and irreversible senescence. Increased expression of the gene encoding the basic helix-loop-helix protein HES1 was required for quiescence to be reversible, because HES1 prevented both premature senescence and inappropriate differentiation in quiescent fibroblasts. In some human tumors, the HES1 pathway was activated, which allowed these cells to evade differentiation and irreversible cell cycle arrest. We conclude that HES1 safeguards against irreversible cell cycle exit both during normal cellular quiescence and pathologically in the setting of tumorigenesis.
| Item Type: | Article or Abstract |
|---|---|
| Additional Information: | This article is available to subscribers only via the URL above. |
| DOI: | 10.1126/science.1155998 |
| PubMed ID: | 18719287 |
| NIHMSID: | NIHMS127942 |
| PMCID: | PMC2721335 |
| Grant Numbers: | R01 CA118043-03, P50 GM071508-05 |
| Keywords or MeSH Headings: | Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism; Cell Aging; Cell Cycle; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p21/metabolism; Fibroblasts/cytology/metabolism; Homeodomain Proteins/genetics/metabolism; Humans; Muscle Development; MyoD Protein/metabolism; Receptors, Notch/metabolism; Recombinant Fusion Proteins/metabolism; Repressor Proteins/genetics/metabolism; Rhabdomyosarcoma/metabolism/pathology; Signal Transduction; Transduction, Genetic; |
| Subjects: | Molecules > Proteins > Transcription factors Cellular and Organismal Processes > Cell Physiology > Cell proliferation Cellular and Organismal Processes > Cell Physiology > Cell cycle |
| Depositing User: | Library Staff |
| Date Deposited: | 25 Jun 2009 20:08 |
| Last Modified: | 07 May 2010 22:33 |
| URI: | http://authors.fhcrc.org/id/eprint/302 |
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