Document Detail

Alternative pathways for the extension of cellular life span: inactivation of p53/pRb and expression of telomerase.
MedLine Citation:
PMID:  10618707     Owner:  NLM     Status:  MEDLINE    
Telomere shortening may be one of several factors that contribute to the onset of senescence in human cells. The p53 and pRb pathways are involved in the regulation of cell cycle progression from G1 into S phase and inactivation of these pathways leads to extension of life span. Short dysfunctional telomeres may be perceived as damaged DNA and may activate these pathways, leading to prolonged arrest in G1, typical of cells in senescence. Inactivation of the p53 and pRb pathways, however, does not lead to cell immortalization. Cells that overcome senescence and have an extended life span continue to lose telomeric DNA and subsequently enter a second phase of growth arrest termed 'crisis'. Forced expression of telomerase in human cells leads to the elongation of telomeres and immortalization. The development of human cancer is frequently associated with the inactivation of the pRb and p53 pathways, attesting to the importance of senescence in restricting the tumor-forming ability of human cells. Cancer cells must also maintain telomere length and, in the majority of cases, this is associated with expression of telomerase activity.
H Vaziri; S Benchimol
Related Documents :
19653337 - Transcriptional down regulation of htert and senescence induction in hepg2 cells by che...
25405767 - Activation of the nlrp3 inflammasome complex is not required for stress-induced death o...
19937137 - Mir-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line throug...
20211237 - Role of endonuclease g in senescence-associated cell death of human endothelial cells.
24656887 - Concurrent estrogen action was essential for maximal progestin effect in oral contracep...
18831007 - Involvement of calpain in the process of jurkat t cell chemotaxis.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Oncogene     Volume:  18     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-14     Completed Date:  2000-01-14     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  7676-80     Citation Subset:  IM    
Stanford University School of Medicine, Department of Molecular Pharmacology, Edward's Building, 300 Pasteur Drive Stanford, California, CA 94305-5332, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Cell Aging*
Cell Cycle
DNA Damage / genetics
Neoplasms / enzymology,  genetics,  pathology
Retinoblastoma Protein / metabolism*
Signal Transduction
Telomerase / antagonists & inhibitors,  metabolism*
Telomere / chemistry,  genetics,  metabolism
Tumor Suppressor Protein p53 / metabolism*
Reg. No./Substance:
0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Mechanisms of switching on p53: a role for covalent modification?
Next Document:  mdm2: a bridge over the two tumour suppressors, p53 and Rb.