Signaling on telomerase: a master switch in cell aging and immortalization.
Cell aging involves damages and losses of genetic materials including the gradual shortening of telomeres. Telomeres, the ends of chromosomes, have a variety of functions, and the most notable ones include those involved in retaining genome integrity and stability and in regulating cell lifespan. Early loss or damage of telomeres causes premature aging, whereas excessive gain of telomeres confers immortality upon some cancer cells. However, the opposing changes in telomere structures and their associated cellular effects on aging and immortalization are forcefully regulated by the enzyme telomerase. Telomerase is a large protein-RNA complex that has telomeric DNA reverse transcriptase activity. Although a wealthy body of information has been obtained on the involvement of telomerase in tumorigenesis, its structure of the holoenzyme, the mode of its action, its cellular function in aging, and the pathways of its regulatory mechanisms have not been entirely understood. Recent research on telomerase has become an increasing investigative effort to uncover the molecular mechanisms of aging and aging-related diseases. This article will briefly review now telomerase may impact aging, what potential in vivo significance the regulation of telomerase may have on aging, how signals are transduced from telomerase and telomere to different cellular effects, and how telomerase itself is controlled in mammalian cells.
Li
He
H
Molecular Signaling Laboratory, Baker Medical Research Institute, Prahran, Victoria, Australia.
Liu
Jun-Ping
JP
D000818:Animals; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence / Q000502:physiology*; D006801:Humans; D015398:Signal Transduction; D019098:Telomerase / Q000378:metabolism* / Q000502:physiology; D016615:Telomere
D019098:Telomerase