1997 Fiscal Year Final Research Report Summary
Genetic regulation of cellular senescence and immortality in cultured human cells.
| Project/Area Number |
08838023
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
老化(加齢)
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| Research Institution | Keio University |
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Principal Investigator |
TAKANO Toshiya Keio Univ.Sch.of Med., Professor, 医学部, 教授 (60051364)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMODA Koji Keio Univ.Sch.of Med., Assist.Prof., 医学部, 講師 (00129470)
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| Project Period (FY) |
1996 – 1997
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| Keywords | cellular senescence / immortalization / type I collagenase gene / regulation of transcription / transcriptional repressor / transcriptional activator / Oct-1 / p33-related tumor suppressor |
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| Research Abstract |
The cellular senescence-associated genes that are repressed in young and immortalized cells are induced in cellular senescence and the senescent phenotypes are mediated by the functions of the senescence-associated genes. One of the senescence-associated genes, the type I collagenase gene, cary two immortaliation-susceptible cis-acting elements, ISEI and ISE2, located in a 100-bp region about 1.7kb upstream. The interplay of two ISE2-binding factors, a putative activator Pluto and a putative repressor Orpheus, was suggested to be crucial for regulation of the collagenase gene accompanying in vitro aging and immortalization.
We isolated three novel cDNA clones as the candidate genes of the transcriptional activator Pluto by one hybrid screening method in yeast. The proteins coded by these cDNA clones conserve the CXXC domain of ALL-1/ML/RX complex that are located at the chromosomal breakpoints of certain leukemic cells. One of the these cDNAs encoded a protein highly related to p33NG1 tumor suppressor.
The senescence-related repressor Orpheus was found to be identical to the transcription factor Oct-1. The Oct-1 protein was co-localized with a component of the nuclear lamina, lamin B,in the nuclear peripheral structure of young and immortalized cells. In senescent cells, the condensation of Oct-1 in the nuclear lamina was disappeared and the Oct-1 protein was diffusely distributed in the whole cells. Oct-1 seemed to repress the cellular senescence-associated genes by forming a heterochromatin-like higher ordered secondary structure of chromatin.
Precise characterization of these immortalization-susceptible factors will give us much information concerning the intrinsic mechanism of in vitro aging and immortalization.
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[Publications] Inada, T., Sugita, T., Dobashi, I., Inagaki, A., Kitao, Y., Matsuda, G., Kato, S., Takano, T., Yagi, G.and Asai, M.: "Dopamine transporter gene polymorphism and psychiatric symptoms seen in schizophrenic patients at their first episode." Am.J.Med.Gen.67. 406-408 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Yamagishi, H., Kato, S., Hiraishi, Y., Ishihara, Y., Hata, J., Matsuo, N.and Takano, T.: "Identification of carriers of Duchenne/Becker muscular dystrophy by a novel method based on deletion of junction fragments in the dystrophin gene." J.Med.Genet.33(12). 1027-1031 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Ohno, Y., Matsuo, K., Suzuki, H., Tanase, H., Serikawa, T., Takano, T.and Saruta, T.: "Genetic linkage of the sarco (endo) plasmic reticulum Ca^<2+>-dependent ATPase II gene tointracellular Ca^<2+> concentration in the spontaneously hypertensive rat." Biochem.Biophys.Res.Commun.227. 789-793 (1996)
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「研究成果報告書概要(欧文)」より
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[Publications] Liu, J., Koyano-Nakagawa, N., Amasaki, Y., Saito-Ohara, F., Ikeuchi, T., Imai, S., Takano, T., Arai, N., Yokota, T.and Arai, K.: "Calcineurin-dependent nuclear translocation of a murine transcription factor NFATx : molecular cloning and functional characterization." Mol.Biol.Cell.8. 157-170 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Shibanuma, M., Mochizuki, E., Maniwa, R., Mashimo, J., Nishiya, N., Imai, S., Takano, T., Oshimura, M.and Nose, K: "Induction of senescence-like phenotypes by forced expression of hic-5, which encodes a novel LIM motif protein, in immortalized human fibroblasts." Mol.Cell.Biol.17(3). 1224-1235 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Inaka, T., Dobashi, I., Sugita, T., Inagaki, A., Kitao, Y., Matsuda, G., Kato, S., Takano, T., Yagi, G.and Asai, M.: "Search for a susceptibility locus to tardive dyskinesia." Hum.Psychopharmacol.12. 35-39 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Ohno, Y., Matsuo, M., Suzuki, H., Tanase, H., Takano, T.and Saruta, T.: "Incresed intracellular Ca^<2+> is not coinherited with with an inferred major gene locus for hypertension (ht) in the spontaneously hypertensive rat." Am.J.Hypertension.10. 282-288 (1997)
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「研究成果報告書概要(欧文)」より
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[Publications] Imai, S., Nishibayashi, S., Takao, K., Tomifuji, M., Fujino, T., Hasagagawa, M.and Takano, T.: "Dissociation of Oct-1 from the nuclear peripheral structure induces the cellular aging-associated collagenase gene expression." Mol.Biol.Cell. 8. 2407-2419 (1997)
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「研究成果報告書概要(欧文)」より
