Functional role of lipid second messenger metabolizing enzyme in cell cycle and stress response

脂质第二信使代谢酶在细胞周期和应激反应中的功能作用

• 批准号: 20390050
• 负责人: GOTO Kaoru
• 金额: $ 12.48万
• 依托单位: Yamagata University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390050/
• 关键词: 細胞周期; ストレス応答; 脂質代謝酵素; アポトーシス; p53; 核; プロテアソーム; イノシトールリン脂質; がん細胞; 細胞組織化学; 酸素グルコース欠乏; 海馬ニューロン; 細胞死

Diacylglycerol kinase (DGK), an enzyme that phosphorylates diacylglycerol to phosphatidic acid, is involved in many pathophysiological cellular responses, such as cancer and apoptosis. Our previous studies show that DGKζ, which contains a nuclear localization signal, is localized in the nucleus of hippocampal neurons but rapidly translocates from the nucleus to the cytoplasm and disappears in the early phase of ischemia, suggesting its implication in an apoptotic process. In this study we investigated the functional link between DGKζ cytoplasmic translocation and p53 that acts as the hub of various stress pathways. We found that cytoplasmic DGKζ induces cytoplasmic localization of p53 after DNA damage and suppresses p53 induction. In neurons, down-regulation of nuclear DGK. after excitotoxic stress leads to aberrant cell cycle reentry, which results in cell death. These findings suggest that DGKζ cytoplasmic translocation exerts distinct effects on signal transduction both in the cytoplasm and the nucleus.

甘油二酯激酶（DGK）是一种将甘油二酯磷酸化为磷脂酸的酶，参与许多病理生理细胞反应，如癌症和细胞凋亡。我们以前的研究表明，DGK β，其中包含一个核定位信号，是定位在海马神经元的核，但迅速从核转位到细胞质，并在缺血的早期阶段消失，这表明它的含义在凋亡过程中。在这项研究中，我们研究了DGK β细胞质易位和p53之间的功能联系，作为各种应激途径的枢纽。我们发现，细胞质DGK-DNase诱导DNA损伤后p53的细胞质定位，并抑制p53的诱导。在神经元中，下调核DGK。在兴奋性毒性应激导致异常的细胞周期重入之后，其导致细胞死亡。这些结果表明，DGK-β胞质易位对细胞质和细胞核中的信号转导都有不同的影响。

项目成果

Diacylglycerol kinase beta promotes dendritic outgrowth and spine maturation in developing hippocampal neurons.

• DOI: 10.1186/1471-2202-10-99
• 发表时间: 2009-08-19
• 期刊: BMC neuroscience
• 影响因子: 2.4
• 作者: Hozumi Y;Watanabe M;Otani K;Goto K
• 通讯作者: Goto K

TIS21/BTG2/PC3 and cyclin D1 are key determinants of nuclear diacylglycerol kinase-zeta-dependent cell cycle arrest

TIS21/BTG2/PC3 和细胞周期蛋白 D1 是核二酰基甘油激酶 Zeta 依赖性细胞周期停滞的关键决定因素

• 发表时间: 2009
• 期刊: Cellular Signaling
• 作者: Evangelisti C;Astolfi A;Gaboardi GC;Tazzari P;Pession A;Goto K;Martelli AM.
• 通讯作者: Martelli AM.

Cytoplasmic localization of diacylglycerol kinase zeta suppresses p53 induction after DNA damage

DNA 损伤后二酰甘油激酶 zeta 的细胞质定位抑制 p53 诱导

• 发表时间: 2012
• 作者: Ozawa T;Tsuruta D;Ikeda K;他;鈴木小夜;楠原洋之 他;Tanaka T
• 通讯作者: Tanaka T

Altered expression of diacylglycerol kinase isozymes in regenerating liver

再生肝脏中二酰甘油激酶同工酶的表达改变

• 发表时间: 2012
• 期刊: Journal of Histchemistry and Cytochemistry
• 作者: T. Nakano;Y. Hozumi;K. Okumoto;K Iseki;T. Saito;S. Kawata;I. Wakabayashi and K. Goto
• 通讯作者: I. Wakabayashi and K. Goto

Cytoplasmic lipid kinase suppresses p53 stability

细胞质脂质激酶抑制 p53 稳定性

• 发表时间: 2009
• 作者: Tanaka T;Okada M;Goto K
• 通讯作者: Goto K