title: Telomerase activation as a repair response to radiation-induced DNA damage in Y79 retinoblastoma cells.
abstract: The molecular mechanism of telomerase activation induced by ionizing radiation (IR) remains poorly understood. We demonstrate that DNA damage induced by IR at doses of 2-5 Gy triggers activation of Akt, predominant to that of protein phosphatase 2A (PP2A), resulting in human telomerase reverse transcriptase (hTERT) phosphorylation and increased telomerase activity in Y79 cells. DNA damage induced by IR at doses greater than 10 Gy might trigger PP2A activation, predominant to that of Akt, resulting in hTERT dephosphorylation and decreased telomerase activity. Our results suggest that differential activation of Akt and PP2A may be responsible for telomerase regulation.
authors.affiliation: Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan; Division of Molecular Genetics, Institute of DNA Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. Electronic address: makiyama@jikei.ac.jp.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Akiyama
authors.forename: Kohji
authors.initials: K
authors.lastname: Ozaki
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawano
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamada
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kawauchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ida
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D004789:Enzyme Activation; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D015870:Gene Expression; D006657:Histones / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D019319:Okadaic Acid / Q000494:pharmacology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012175:Retinoblastoma; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; C468783:H2AX protein, human; D006657:Histones; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019319:Okadaic Acid; C509186:TERT protein, human; D019098:Telomerase; D000077191:Wortmannin
keywords: DNA damage response; Human telomerase reverse transcriptase; Ionizing radiation; Retinoblastoma; Telomerase