Upregulation of telomerase activity by X-irradiation in mouse leukaemia cells is independent of Tert, Terc, Tnks and Myc transcription.
X-irradiation of two mouse myeloid leukaemia cell lines was found to lead to increased telomerase activities. Maximal increases in activity at 24 h post-irradiation were approximately three times control unirradiated cell levels. These maxima were reached at between 3-5 Gy depending upon cell line. Peak activity was reached at 8h, remained elevated to 24 h and returned to control levels by 48 h. In contrast, X-irradiation did not activate telomerase in a telomerase-negative human fibroblast line, while in cultured normal mouse bone marrow cells irradiation appeared to reduce activities. No simple relationship between radiation-induced increases in telomerase activity in the myeloid leukaemia lines and the proportions of cells in the S or M phases of the cell cycle was apparent. Radiation-induced increases in activity were significantly reduced by inhibitors of transcription (actinomycin D, alpha-amanatin) and protein synthesis (cycloheximide). These data are consistent with two possibilities: (i) X-irradiation leads to increased transcription and/or translation of a component of telomerase, thus increasing activities; or (ii) X-irradiation induces the transcription of a positive regulator of telomerase activity. Northern blot analysis did not indicate that transcription of mTert, the catalytic subunit of telomerase, or mTerc, the RNA component, was elevated after irradiation. Similarly, no significant changes in the expression of Myc or Tnks, the tankyrase gene, two suspected telomerase regulators, were detected. These data are therefore consistent with the induction by X-irradiation of a positive regulator of telomerase activity other than Tnks or Myc or the core protein and RNA components of the enzyme.
Finnon
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Radiation Effects Department, National Radiological Protection Board, Chilton, Didcot, Oxon OX11 ORQ, UK.
Silver
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Bouffler
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D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins; D004307:Dose-Response Relationship, Radiation; D004790:Enzyme Induction / Q000187:drug effects; D007951:Leukemia, Myeloid / Q000201:enzymology*; D051379:Mice; D008808:Mice, Inbred CBA; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D012313:RNA; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014965:X-Rays
D004268:DNA-Binding Proteins; D016271:Proto-Oncogene Proteins c-myc; C422952:telomerase RNA; D012313:RNA; D003513:Cycloheximide; C509186:TERT protein, human; D019098:Telomerase; C509187:Tert protein, mouse