Characterization of the molecular mechanisms of Akt activation

Akt 激活分子机制的表征

• 批准号: 17370044
• 负责人: NOGUCHI Masayuki
• 金额: $ 10.03万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17370044/
• 关键词: Gene; Cancer; Enzyme reaction; Nucleic acid; Protein; 生体分子

Serine threonine kinase Akt, also called PKB (Protein Kinase B), plays a central role in the regulation of intracellular survival. Deregulation of this Akt signaling pathway underlies various human neoplastic diseases. Recently, the protooncogene TCL1 (T cell leukemia 1), with a previously unknown physiological function, was shown to interact with the Akt pleckstrin homology domain, enhancing Akt kinase activity; hence, it functions as an Akt kinase co-activator. In contrast to pathological conditions in which the TCL1 gene is highly activated in various human neoplasmic diseases, the physiological expression of TCL1 is tightly limited to early developmental cells as well as various developmental stages of immune cells. The NBRE (Nerve Growth Factor Responsive Element) of the proximal TCL1 promoter sequences can regulate the restricted physiological expression of TCL1 in a negative feedback mechanism. Further, based on the NMR structural studies of Akt-TCL1 protein complexes, an inhibitory peptide, "Akt-in," consisting of the βA strand of TCL1, has been identified and has therapeutic potential. Our study together promote substantial understanding of TCL1-Akt functional interaction and the biological action of the protooncogene TCL1 family and the new suppressive drug specific for Akt, a core intracellular survival regulator.

丝氨酸苏氨酸激酶Akt，又称PKB(Protein Kinase B)，在细胞内存活的调控中起着核心作用。Akt信号通路的失控是多种人类肿瘤疾病的基础。最近，原癌基因TCL1(T细胞白血病1)被证明与Akt的pleckstrin同源结构域相互作用，增强Akt激酶的活性，从而起到Akt激酶共激活的作用。与TCL1基因在各种人类肿瘤疾病中高度激活的病理条件不同，TCL1的生理表达严格限制在早期发育的细胞以及不同发育阶段的免疫细胞。TCL1启动子序列的神经生长因子反应元件(NBRE)以负反馈机制调控TCL1的限制性生理表达。此外，基于对Akt-Tcl1蛋白复合体的核磁共振结构研究，已鉴定出一种由Tcl1的βA链组成的抑制肽“Akt-in”，并具有治疗潜力。我们的研究共同促进了对TCL1-Akt功能相互作用的深入了解，以及原癌基因TCL1家族和针对Akt的新抑制药物的生物学作用。Akt是一种核心的细胞内生存调节因子。

项目成果

The roles of the PI3K-AKT network in infectious Diseases.

PI3K-AKT 网络在传染病中的作用。

• 发表时间: 2008
• 期刊: Jpn J. Infect Dis. (In press)
• 作者: 植木龍也;T.Ueki;M.Yoshinaga;T.Ueki;N.Kawakami;道端齊;M.Yoshihara;H.Michibata;M. Noguchi
• 通讯作者: M. Noguchi

Fusion of Biotechnology and Biology

生物技术与生物学的融合

• 发表时间: 2007
• 期刊: Hokkaido University Press
• 作者: 植木龍也;T.Ueki;M.Yoshinaga;T.Ueki;N.Kawakami;道端齊;M.Yoshihara;H.Michibata;M. Noguchi;M. Noguchi;M. Noguchi
• 通讯作者: M. Noguchi

細胞死と増殖を介した生体ホメオスターシス制御の破綻と疾病

通过细胞死亡和增殖破坏生物稳态控制和疾病

• 发表时间: 2007
• 作者: 植木龍也;T.Ueki;M.Yoshinaga;T.Ueki;N.Kawakami;道端齊;M.Yoshihara;H.Michibata;M. Noguchi;M. Noguchi;M. Noguchi;M. Hiromura;M. Noguchi;M. Noguchi;野口 昌幸
• 通讯作者: 野口 昌幸

バイオとナノの融合〔新生命科学の融合〕

生物与纳米的融合【新生命科学的融合】

• 发表时间: 2007
• 作者: 植木龍也;T.Ueki;M.Yoshinaga;T.Ueki;N.Kawakami;道端齊;M.Yoshihara;H.Michibata;M. Noguchi;M. Noguchi;M. Noguchi;M. Hiromura;M. Noguchi;M. Noguchi;野口 昌幸;M. Noguchi;野口 昌幸;野口 昌幸;野口昌幸
• 通讯作者: 野口昌幸

Identification of NBRE (nerve growth factor responsive element) of the TCL1 promoter as a novel negative regulatory element.

鉴定 TCL1 启动子的 NBRE（神经生长因子反应元件）为新型负调控元件。

• 发表时间: 2006
• 期刊: J. Biol. Chem. 281
• 作者: 植木龍也;T.Ueki;M.Yoshinaga;T.Ueki;N.Kawakami;道端齊;M.Yoshihara;H.Michibata;M. Noguchi;M. Noguchi;M. Noguchi;M. Hiromura
• 通讯作者: M. Hiromura