| Telomerase, checkpoints and cancer. | |
| | |
MedLine Citation:
|
PMID: 9338104 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Telomere dynamics and changes in telomerase activity are consistent elements of cellular alterations associated with changes in proliferative state. In particular, the highly specific correlations and early causal relationships between telomere loss in the absence of telomerase activity and replicative senescence or crisis, on the one hand, and telomerase reactivation and cell immortality, on the other, point to a new and important paradigm in the complementary fields of ageing and cancer. Although the signalling pathways between telomeres and transcriptional and cell cycle machinery remain undefined, recently described homologies between telomeric proteins and lipid/protein kinase activities important in chromosome stability provide evidence for the existence of pathways transducing signals originating in chromosome structure to cell cycle regulatory processes. Similarities between cell cycle arrest at senescence and the response of mortal cells to DNA/oxidative damage suggest overlap in the signal transduction mechanisms culminating in irreversible and stable cell cycle arrest. The feasibility of targeting telomeres/telomerase as a strategy for antiproliferative therapeutics has been shown in studies in yeast, in which mutations in specific telomere associated genes result in delayed cell death. Similarly, antisense oligonucleotide inhibition of telomerase activity in human tumour cells (HeLa) results in delayed cell death. The mechanism of cell death and possible escape from this fate require further study. In human cells, however, it would seem reasonable to predict that in these circumstances, apoptosis is induced in the vast majority of cells either directly in response to a DNA damage signal arising from critically shortened telomeres or as a secondary consequence of genetic instability. |
| | |
Authors:
|
C B Harley; S W Sherwood |
Related Documents
:
|
9028834 - Generation of a human melanocyte cell line by introduction of hpv16 e6 and e7 genes. 19733384 - Large cell change of hepatocytes in chronic viral hepatitis represents a senescent-rela... 17395154 - Quantitative proteomic analysis of human breast epithelial cells with differential telo... 21414204 - Atf3, an htlv-1 bzip factor binding protein, promotes proliferation of adult t-cell leu... 11157244 - Cell cycle regulation by light in prochlorococcus strains. 3045114 - Reassessment of the translocation hypothesis by kinetic studies on hexose transport in ... |
Publication Detail:
|
Type: Journal Article; Review |
Journal Detail:
|
Title: Cancer surveys Volume: 29 ISSN: 0261-2429 ISO Abbreviation: Cancer Surv. Publication Date: 1997 |
Date Detail:
|
Created Date: 1997-11-14 Completed Date: 1997-11-14 Revised Date: 2009-11-19 |
Medline Journal Info:
|
Nlm Unique ID: 8218015 Medline TA: Cancer Surv Country: UNITED STATES |
Other Details:
|
Languages: eng Pagination: 263-84 Citation Subset: IM |
Affiliation:
|
Geron Corporation, Menlo Park, CA 94025, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aging
/
genetics*,
physiology Apoptosis Cell Aging / genetics*, physiology Cell Cycle / physiology Cyclin-Dependent Kinases / metabolism DNA Damage / genetics Genes, p53 Humans Neoplasms / etiology, genetics*, physiopathology Signal Transduction Telomerase / metabolism* Telomere / genetics*, physiology |
| Chemical | |
Reg. No./Substance:
|
EC 2.7.11.22/Cyclin-Dependent Kinases; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Functions of the DNA dependent protein kinase.
Next Document: The ATM gene and protein: possible roles in genome surveillance, checkpoint controls and cellular de...