1996 Fiscal Year Final Research Report Summary
cDNA cloning of cellular aging and cellular senescence
| Project/Area Number |
07672362
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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 |
Biological pharmacy
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| Research Institution | Hiroshima University |
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Principal Investigator |
IDE Toshinori Hiroshima University School of Medicine, Professor, 医学部, 教授 (60012746)
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| Co-Investigator(Kenkyū-buntansha) |
TAHARA Hidetoshi Hiroshima University School of Medicine, Research Associate, 医学部, 助手 (00271065)
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| Project Period (FY) |
1995 – 1996
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| Keywords | cellular senescence / cell immortality / senescence gene / immortality gene / cDNA library / differential screening |
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| Research Abstract |
Human normal somatic cells have a limited proliferative lifespan. Cells transformed with T antigen of DNA tumor viruses can extend their proliferative lifespan, but do not proliferate indefinitely and eventually die. Previous studies indicated that 1) phenotype of limited proliferative lifespan is dominant over that of unlimited proliferative lifespan, 2) senescent cells at the end of proliferative lifespan inhibit DNA synthesis in nuclei from young growing cells after cell fusion, and finally 3) life-extended transformed cells cease proliferation immediately after inactivation of T antigen. These and other results suggested that the cells accumulate proliferation-inhibitory factor with increasing proliferative age. In this project we search for cDNAs which accumulate in senescent normal and life-extended transformed cells compared with in young normal and immortalized cells. From differential hybridization screening of cDNA library from human fibroblasts which was transformed and proliferating in life-extended stage revealed several candidate cDNAs. One of these, named N10 clone, accumulated in normal senescent and life-extended cells compared with normal young and immortalized cells. Full length of N10 was consisted of 1272 bp which had a possible open reading frame of 232 amino acid. This peptide was rich in hydrophilic amino acids and had such characteristic structure of a typical transcription factor as basic region follwed by leucine zipper. When full length cDNA was connected under expression promotor and transfected into young fibroblasts, premature senescence occurred in some of transfected clones. Northern blot suggested that premature senescence and expression level of N10 was correlated. N10 is one of candidate cDNA which functions in cellular senescence.
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