量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum Science and Technology.
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PIDD (p53-induced protein with a death domain) plays a critical role in the activation of caspase-2 to trigger apoptosis induced by DNA damage through the formation of a so-called PIDDosome, which contains the adaptor protein RAIDD and caspase-2. We found that transcription of PIDD was induced after exposure to ionizing radiation in rat small intestinal epithelial cell line (IEC6) cells. Yeast two-hybrid analysis indicated that the death domain of rat PIDD interacts with RAIDD. Interestingly, a rat C-terminal PIDD fragment (residues 773-917) containing the death domain interacts with RAIDD much more tightly than the longer PIDD fragment (residues 610-917). When the PIDD (773-917) fragment was overexpressed in theses cells, the PIDD-mediated activation of caspase-2 was dominant-negatively inhibited. In order to use the PIDD (773-917) fragment as an anti-apoptotic drug, we purified a recombinant PIDD (773-917) fragment fused with a basic 11-amino acid peptide derived from the HIV-Tat protein which facilitates uptake of the protein into mammalian cells with high efficiency. When PIDD (773-917)-TAT was added to the IEC6 cells, the protein was efficiently delivered into the cells within an hour. Furthermore, we observed that ionizing radiation-induced activation of caspase-2 and caspase-9 was inhibited when PIDD (773-917)-TAT was added to the IEC6 cells. These results suggest that PIDD (773-917)-TAT could protect gastrointestinal cells from ionizing radiation-induced cell death.
第32回日本分子生物学会年会
