Study on the regulatory mechanism of p53 transactivation by clathrin heavy chain

网格蛋白重链对p53反式激活的调控机制研究

• 批准号: 17013088
• 负责人: ENARI Masato
• 金额: $ 35.9万
• 依托单位: National Cancer Center Research Institute and Research Center for Innovative Oncology, National Cancer Center Hospital East
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17013088/
• 关键词: 癌; 放射線; p53; クラスリン; エンドサイトーシス; NuMA; ALK; アクチン; Gas41; Leading Ede; EGF; 細胞運動; 転移; p300

We have previously identified clathrin heavy chain as a p53-binding protein. In this study, CHC is present in nuclei and promotes p53 transactivation through the enhancement of the interaction between p53 and p300, histone acetyltransferase. We also identified nuclear mitotic apparatus (NuMA)as a nuclear CHC-binding factor and showed that NuMA was a critical determinant for p53-transcriptional selectivity mediated by Cdk8. Moreover, the structural model of CHC-p53 interaction was constructed and an amino acid residue in CHC, which is important for p53 transactivation, was identified. Plasma membrane-associated p53 is involved in the regulation of CHC-dependent endocytosis and actin-mediated cell motility.

我们之前已经鉴定出网格蛋白重链是一种p53结合蛋白。在本研究中，CHC存在于细胞核中，通过增强p53与组蛋白乙酰转移酶p300之间的相互作用，促进p53的反式活化。我们还发现核有丝分裂装置（NuMA）是核chc结合因子，并表明NuMA是Cdk8介导的p53转录选择性的关键决定因素。此外，构建了CHC-p53相互作用的结构模型，并鉴定了CHC中一个对p53反活化很重要的氨基酸残基。质膜相关p53参与chc依赖性内吞作用和肌动蛋白介导的细胞运动的调节。

项目成果

Requirement of clathrin heavy chain for p53-mediated transcription

• DOI: 10.1101/gad.1381906
• 发表时间: 2006-05-01
• 期刊: GENES & DEVELOPMENT
• 影响因子: 10.5
• 作者: Enari, M;Ohmori, K;Taya, Y
• 通讯作者: Taya, Y

p53-mdmx相互作用を阻害する低分子抗がん剤

抑制p53-mdmx相互作用的小分子抗癌药物

• 发表时间: 2010

チロシンキナーゼALKによるp53を介した転写の抑制機構

酪氨酸激酶 ALK 对 p53 介导的转录的抑制机制

• 发表时间: 2009
• 作者: 江成政人;吉田祐輔;横田淳;田矢洋一
• 通讯作者: 田矢洋一

Hedgehog signaling overrides p53-mediated tumor suppression by activating Mdm2

• DOI: 10.1073/pnas.0712216105
• 发表时间: 2008-03-25
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Abe, Yoshinori;Oda-Sato, Eri;Tanaka, Nobuyuki
• 通讯作者: Tanaka, Nobuyuki

Preferences in phosphorylation sites in the retinoblastoma protein between D-type cyclin-dependent kinases, Cdk4 and Cdk6 in vitro.

体外 D 型细胞周期蛋白依赖性激酶、Cdk4 和 Cdk6 之间视网膜母细胞瘤蛋白磷酸化位点的偏好。

• 发表时间: 2005
• 期刊: J. Biochem. 137
• 作者: Takai T;Fukasawa K;Suzuki-Takahashi I;Semba K;Kitagawa M;Taya Y;Hirai H
• 通讯作者: Hirai H