The Introduction of Dominant-Negative p53 Mutants Suppresses Temperature Shift-Induced Senescence in Immortal Human Fibroblasts Expressing a Thermolabile SV40 Large T Antigen.
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概要
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Immortal human fibroblasts, SVts8 cells, which express a heat-labile SV40 large T antigen, induces a senescence-like phenomenon in response to upward shift in temperature. Cells with arrested division show strong induction of senescence-associated β-galactosidase. We examined how p53 and pRB are involved in this phenomenon since they are major targets of the T antigen. Transfection of cells with plasmids encoding the wild-type T antigen or human papilloma virus type 16 E6/E7 proteins completely abolished the arrest in cell division, a plasmid encoding the E6 protein suppressed it markedly, while a plasmid encoding E7 had no effect. Plasmids encoding dominant-negative p53 mutants also suppressed the arrest in cell division to various degrees. Upon temperature shift, p21 mRNA was upregulated 10-fold in SVts8 cells, but only slightly in clones expressing the wild-type T antigen or dominant-negative p53 mutants. These data demonstrate that p53 plays a major role in this senescence-like phenomenon.
著者
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Fujii Michihiko
Kihara Inst. For Biological Res. And Graduate School Of Integrated Sci. Yokohama City Univ.
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Nakabayashi Kazuhiko
Kihara Institute For Biological Research Yokohama City University
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Ayusawa Dai
Kihara Inst. For Biological Res. And Graduate School Of Integrated Sci. Yokohama City Univ.
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OGINO Hideki
Kihara Institute for Biological Research and Graduate School of Integrated Science, Yokohama City Un
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IDE Akiko
Kihara Institute for Biological Research, Yokohama City University
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JOGUCHI Atsuhiro
Kihara Institute for Biological Research, Yokohama City University
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Joguchi Atsuhiro
Kihara Institute For Biological Research Yokohama City University
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