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Studies of the molecular mechanisms in the regulation of telomerase activity
Author(s) -
LIU JUNPING
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.15.2091
Subject(s) - telomerase , telomere , biology , telomerase rna component , microbiology and biotechnology , telomerase reverse transcriptase , cell division , somatic cell , cancer cell , dna replication , senescence , gene , cell , genetics , cancer
Telomerase, a specialized RNA‐directed DNA polymerase that extends telomeres of eukaryotic chromosomes, is repressed in normal human somatic cells but is activated during development and upon neoplasia. Whereas activation is involved in immortalization of neoplastic cells, repression of telomerase permits consecutive shortening of telomeres in a chromosome replication‐dependent fashion. This cell cycle‐dependent, unidirectional catabolism of telomeres constitutes a mechanism for cells to record the extent of DNA loss and cell division number; when telomeres become critically short, the cells terminate chromosome replication and enter cellular senescence. Although neither the telomere signaling mechanisms nor the mechanisms whereby telomerase is repressed in normal cells and activated in neoplastic cells have been established, inhibition of telomerase has been shown to compromise the growth of cancer cells in culture; conversely, forced expression of the enzyme in senescent human cells extends their life span to one typical of young cells. Thus, to switch telomerase on and off has potentially important implications in anti‐aging and anti‐cancer therapy. There is abundant evidence that the regulation of telomerase is multifactorial in mammalian cells, involving telomerase gene expression, post‐translational protein‐protein interactions, and protein phosphorylation. Several protooncogenes and tumor suppressor genes have been implicated in the regulation of telomerase activity, both directly and indirectly; these include c‐Myc, Bcl‐2, p21 WAF1 , Rb, p53, PKC, Akt/PKB, and protein phosphatase 2A. These findings are evidence for the complexity of telomerase control mechanisms and constitute a point of departure for piecing together an integrated picture of telomerase structure, function, and regulation in aging and tumor development—Liu, J.‐P. Studies of the molecular mechanisms in the regulation of telomerase activity. FASEB J. 13, 2091–2104 (1999)