京都大学 · 生化学・遺伝学・分子生物学
伊賀津教授の研究室では、細胞死と細胞競争の分子メカニズムに焦点を当て、特にDrosophilaをモデル生物として、アポトーシスの制御因子やERストレスが細胞競争に与える影響を解明しています。Bcl-2ファミリーの新規因子Drob-1の同定や、DIAP1の機能、ならびにエンドプラズミックリティクルストレスが細胞競争を誘導するメカニズムの解明が進んでいます。これらの研究は、がんの発症や組織の恒常性を保つ仕組みの理解に貢献しています。
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The Bcl-2/CED-9 family of proteins, which includes both antiapoptotic and proapoptotic members, plays key regulating roles in programmed cell death. We report here the identification and characterization of Drob-1, the first Drosophila member of the Bcl-2/CED-9 family to be isolated. Drob-1 contains four conserved Bcl-2 homology domains (BH1, BH2, BH3, and BH4) and a C-terminal hydrophobic domain. Ectopic expression of Drob-1 in the developing Drosophila eye resulted in a rough-eye phenotype. Fu
Members of the inhibitor of apoptosis protein (IAP) family can inhibit caspases and cell death in a variety of insect and vertebrate systems. Drosophila IAP1 (DIAP1) inhibits cell death to facilitate normal embryonic development. Here, using RNA interference, we showed that down-regulation of DIAP1 is sufficient to induce cell death in Drosophila S2 cells. Although this cell death process was accompanied by elevated caspase activity, this activation was not essential for cell death. We found tha
Cell competition is a context-dependent cell elimination through short-range cell-cell interaction, in which cells with higher fitness eliminate neighboring less-fit or oncogenic cells within the growing tissue. Cell competition can be triggered by many different factors such as heterozygous mutations in the ribosomal protein genes (which are called "Minute" mutations), elevated Myc, Yorkie/YAP, Wg/Wnt, JAK-STAT, Ras, or Src activity, and loss of Mahjong/VprBP, endocytic pathway components, or a
Cell competition is a context-dependent cell elimination via cell-cell interaction whereby unfit cells ('losers') are eliminated from the tissue when confronted with fitter cells ('winners'). Despite extensive studies, the mechanism that drives loser's death and its physiological triggers remained elusive. Here, through a genetic screen in Drosophila, we find that endoplasmic reticulum (ER) stress causes cell competition. Mechanistically, ER stress upregulates the bZIP transcription factor Xrp1,
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