Regulation of p53 pathway and Tumor Growth by Novel Nucleolar Protein PICT1

新型核仁蛋白 PICT1 对 p53 通路和肿瘤生长的调节

• 批准号: 21790204
• 负责人: KAWAHARA Kohichi
• 金额: $ 2.75万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790204/
• 关键词: 細胞増殖; 細胞死; p53経路; 癌; がん

The tumor-suppressive MDM2-p53 intracellular signaling pathway is activated by cellular stress. Such stress includes DNA damage, which triggers the ATM-Chk2 and ATR-Chk1 cascades ; infection or oncogene activation, which induce t he p19ARF pathway ; and nucleolar stress, which initiates a cascade mediated by ribosomal proteins (RPs), particularly RPL5, RPL11, RPL23, and RPS7. These RPs are usually located in the nucleolus but are rapidly released into the nucleoplasm upon nucleolar stress, activating the MDM2-p53 pathway. However , it is unknown whether there are direct connections between p53-activating RP genes and cancer development in vivo, and which mechanism these RPs emplo y to translocate from the nucleolus to the nucleoplasm in response to stress . Using in vivo and in vitro experiments involving both human and murine tissues, we show that novel gene, Pict1, is a key regulator that acts thro ugh RP to control MDM2-p53 responses to nucleolar stress. In addition, Pict1 expression correlates with human colon cancer progression in human.

肿瘤抑制性MDM 2-p53细胞内信号传导途径被细胞应激激活。这种应激包括DNA损伤，其触发ATM-Chk 2和ATR-Chk 1级联;感染或癌基因激活，其诱导p19 ARF通路;以及核仁应激，其启动由核糖体蛋白（RP），特别是RPL 5，RPL 11，RPL 23和RPS 7介导的级联。这些RP通常位于核仁中，但在核仁应激时迅速释放到核质中，激活MDM 2-p53途径。然而，目前尚不清楚p53激活的RP基因与体内癌症发展之间是否存在直接联系，以及这些RP响应于应激而从核仁移位到核质的机制。利用涉及人和小鼠组织的体内和体外实验，我们表明新基因Pict 1是通过RP控制MDM 2-p53对核仁应激反应的关键调节因子。此外，Pict 1表达与人类结肠癌进展相关。

项目成果

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Regulation of the MDM2-P53Pathway and Tumor Growth by PICT1/GLTSCR2via Nucleolar RPL11

PICT1/GLTSCR2 通过核仁 RPL11 调节 MDM2-P53 通路和肿瘤生长

• 期刊: Nature Medicine in press
• 作者: Masato Sasaki;Kohichi Kawahara;Miki Nishio;Koshi Mimori;Ryunosuke Kogo;Koichi Hamada;Bunsho Itoh;Jia Wang;Yukako Komatsu;Yong Ryoul Yang;Hiroki Hikasa;Yasuo Horie;Takayuki Yamashita;Takehiko Kamijo;Yanping Zhang;Yan Zhu;Carol Prives;Toru
• 通讯作者: Toru

Idetification of a novel gene PICT1/GLTSCR2 which regulates MDM2-p53 pathway and tumor growth

鉴定调节 MDM2-p53 通路和肿瘤生长的新基因 PICT1/GLTSCR2

• 发表时间: 2010
• 作者: 河原康一、鈴木聡;ら
• 通讯作者: ら

The role of the tumorsuppressor gene MATS1(Mob1) in the Hipposignaling pathway

肿瘤抑制基因 MATS1(Mob1) 在 Hipposignaling 通路中的作用

• 发表时间: 2010
• 作者: 西尾美希;濱田浩一;佐々木雅人;伊東文祥;王嘉;小西弘晃;河原康一;佐々木雄彦;鈴木聡
• 通讯作者: 鈴木聡

Suppression of onset and development of cancer by suppressing PICT1, and PICT1 as prognostic marker of cancer patients.

通过抑制PICT1来抑制癌症的发生和发展，并将PICT1作为癌症患者的预后标志物。

• 发表时间: 2010