p73およびΔNp73の安定性によるp53の分子機構と発がん

• 研究課題/領域番号: 15023264
• 研究種目: 特定領域研究
• 配分区分: 補助金
• 審査区分: 生物系
• 研究機関: 千葉県がんセンター研究所
• 研究代表者: 中川原 章 千葉県がんセンター, 生化学研究部, 部長 (50117181)
• 研究分担者: 尾崎 俊文 千葉県がんセンター, 生化学研究部, 上席研究員 (40260252)
• 研究期間 (年度): 2003
• 研究課題ステータス: 完了 (2003年度)
• 配分額: 6,400千円 (直接経費: 6,400千円); 2003年度: 6,400千円 (直接経費: 6,400千円)
• キーワード: p53 / p73 / ユビキチンリガーゼ / NEDL2 / UFD2a / プロテアゾーム

研究概要

発がんとがんの進展におけるp73,ΔNp73およびp53の安定化を介した分子制御機構に関し、以下のことを明らかにした。神経芽腫cDNAライブラリーからクローニングした新規HECT型E3ユビキチンリガーゼNEDL2は、そのWWドメインを介してp73のカルボキシ末端に存在するPYモチーフを含む領域と物理的に結合し、p73のポリユビキチン化を促進した。しかし、p73は分解されることなく逆に安定化され、転写因子としての活性が亢進された。NEDL2のp53との結合は見られなかった。一方、神経芽腫細胞株において我々が見いだした1p36領域のホモ欠失領域にマップされたE3/E4ユビキチンリガーゼUFD2aは、p73とSAMドメインを介して特異的に結合したが、それをポリユビキチン化する機能は極めて弱かったものの、p73の蛋白分解を促進した。したがって、UFD2aは主にプロテアゾーム以外の分解機構によってp73の分解を促進している可能性が示された。

研究成果

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