Document Detail


Regulatory mechanisms of replication growth limits in cellular senescence.
MedLine Citation:
PMID:  9343977     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Normal human diploid fibroblasts cannot divide indefinitely in culture. At the end of their lifespan they withdraw from the cell cycle permanently by a process termed cellular senescence. Recent molecular studies indicate that upregulation of two inhibitors of cyclin-dependent kinases, p16 and p21, is responsible for blocking the G1/S transition in senescent cells. Although the state of senescence resembles terminal differentiation in that both exhibit irreversible growth arrest and resistance to apoptosis, other molecular changes are seen only in senescent cells. This suggests that the signal pathway specific for senescence is present in normal cells. Changes in chromosomes, such as progressive shortening of the telomeres and erosive damage by detrimental by-products in metabolism, may be the signals that trigger senescence, leading to the inactivation of cell cycle progression. On the other hand, it seems that a dominant genetic program is intrinsically preset to ensure a growth limit in the normal cell. This notion is supported by cell fusion and microcell transfer experiments which show that escaping from senescence requires recessive mutations in senescence-specific genes. Identification of these participating genes and clarification of their mode of action will provide the basis for understanding the mechanisms governing the differences between mortality in normal cells and immortality in cancer cells.
Authors:
Z F Chang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Journal of the Formosan Medical Association = Taiwan yi zhi     Volume:  96     ISSN:  0929-6646     ISO Abbreviation:  J. Formos. Med. Assoc.     Publication Date:  1997 Oct 
Date Detail:
Created Date:  1997-11-13     Completed Date:  1997-11-13     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9214933     Medline TA:  J Formos Med Assoc     Country:  TAIWAN    
Other Details:
Languages:  eng     Pagination:  784-91     Citation Subset:  IM    
Affiliation:
Institute of Biochemistry, National Taiwan University, College of Medicine, Taipei, ROC.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Cell Aging*
Cell Division
Chromosome Aberrations
Cyclin-Dependent Kinase Inhibitor p16 / physiology
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / physiology
G1 Phase
Humans
Chemical
Reg. No./Substance:
0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins

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