Control of the Reversibility of Cellular Quiescence by the Transcriptional Repressor HES1

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 peri...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2008-08, Vol.321 (5892), p.1095-1100
Main Authors: Sang, Liyun, Coller, Hilary A, Roberts, James M
Format: Article
Language:English
Subjects:
B lymphocytes
Basic Helix-Loop-Helix Transcription Factors - genetics
Basic Helix-Loop-Helix Transcription Factors - metabolism
Biological and medical sciences
Cell Cycle
Cell cycle, cell proliferation
Cell Differentiation
Cell division
Cell fusion
Cell growth
Cell Line
Cell Line, Tumor
Cell lines
Cell physiology
Cell Proliferation
Cells
Cellular biology
Cellular differentiation
Cellular Senescence
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
Fibroblasts
Fibroblasts - cytology
Fibroblasts - metabolism
Fundamental and applied biological sciences. Psychology
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Molecular and cellular biology
Muscle Development
MyoD Protein - metabolism
Receptors, Notch - metabolism
Recombinant Fusion Proteins - metabolism
Repressor Proteins - genetics
Repressor Proteins - metabolism
Rhabdomyosarcoma - metabolism
Rhabdomyosarcoma - pathology
Signal Transduction
Stem cells
Transcription Factor HES-1
Transduction, Genetic
Tumors
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1155998