Cdk Binding Protein

Cdk结合蛋白

• 批准号: 13043002
• 负责人: TOYOSHIMA Hideo
• 金额: $ 47.68万
• 依托单位: University of Tsukuba
• 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: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13043002/
• 关键词: CDKinhibitor; cell cycle; cyclin; cyclindependent kinase (cdk); SREBP; cell differentiation; DNA replication; lipid metabolism; CDK; CDK阻害因子; p21; Cdtl; Geminin; Cdt1; p57; Ceb; Myc; p53; LIM Kinase; Cdk

Search for interacting proteins of p57CDK inhibitor revealed that p57 binds to LIM kinase-1, a key regulator of actin filament under G-protein signaling cascade. p57 turned out to control not only cell cycle but also cytoskeleton and cell differentiation through binding to LIM kinase-1 by translocating the protein from cytoplasms to nucleus. Transgenic mice expressing SREBP (sterol regulatory element binding protein), a master regulator of lipid metabolism, specifically in liver turned out to show massive liver enlargement. Further analysis showed that SREBP directly induces the transcriptional expression of p21CDK inhibitor, thus may controls not only lipid metabolism but also cell cycle and cell proliferation.Human diploid fibroblasts (HDF) rarely, if ever, undergo spontaneous transformation to an immortalized cell type. We observed the immortalization of an HDF cell line following transduction with cyclin A2 or cdkl genes via retroviral vectors. Cytogenetic studies revealed that the immortal lines share common chromosomal aberrations. FISH studies revealed frequent loss or translocations of one copy of tumor suppressor genes, relative to the parental cells. Deregulated expression of cyclin A2 or cdkl appeared to enhance the immortalization of the HDF through the induction of chromosomal aberrations.

对p57 CDK抑制剂相互作用蛋白的研究表明，p57与LIM激酶1结合，LIM激酶1是G蛋白信号级联中肌动蛋白丝的关键调节因子。p57通过与LIM激酶1结合，将LIM激酶1从细胞内转移到细胞核，不仅控制细胞周期，而且控制细胞骨架和细胞分化。转基因小鼠表达SREBP（固醇调节元件结合蛋白），脂质代谢的主要调节剂，特别是在肝脏显示出巨大的肝脏肿大。进一步的研究表明，SREBP直接诱导p21 CDK抑制因子的转录表达，从而不仅调控脂质代谢，而且调控细胞周期和细胞增殖。我们观察到HDF细胞系的永生化后，通过逆转录病毒载体与细胞周期蛋白A2或cdk1基因转导。细胞遗传学研究表明，不朽线共享共同的染色体畸变。FISH研究显示，相对于亲本细胞，肿瘤抑制基因的一个拷贝经常丢失或易位。细胞周期蛋白A2或cdkl的表达失调似乎通过诱导染色体畸变增强HDF的永生化。

项目成果

Immortalization in a normal foreskin fibroblast culture following transduction of cyclin A2 and cdkl genes in retrovirus vectors.

在逆转录病毒载体中转导细胞周期蛋白A2和cdk1基因后，在正常包皮成纤维细胞培养物中永生化。

• 发表时间: 2004
• 期刊: Biochem. Biophys. Res. Commun. 316
• 作者: 井上訓之;Nobuyuki Inoue;Inoue N;Takahashi A;Takahashi A;内田早苗;Ping Luo;内田早苗;Ping Luo
• 通讯作者: Ping Luo

Toyoshima H 他: "p57Kip2 regulates actin dynamics by binding and translocating LIM-kinase 1 to the nucleus"Journal of Biological Chemistry. 278(52). 52919-52923 (2003)

Toyoshima H 等人：“p57Kip2 通过将 LIM 激酶 1 结合并易位至细胞核来调节肌动蛋白动力学”，《生物化学杂志》278(52) (2003)。

Ohtsubo M 他: "Nuclear export signal in CDC25B"Biochem Biophys Res Commun.. 316(1). 226-232 (2004)

Ohtsubo M 等人：“CDC25B 中的核输出信号”Biochem Biophys Res Commun. 316(1) (2004)。

Immortalization in a normal foreskin fibroblast culture following transduction of cyclin A2 and cdkl genes in retrovirus vectors

在逆转录病毒载体中转导细胞周期蛋白A2和cdkl基因后，正常包皮成纤维细胞培养物中的永生化

• 发表时间: 2004
• 期刊: Exp. Cell Res. 294
• 作者: 井上訓之;Nobuyuki Inoue;Inoue N;Takahashi A;Takahashi A;内田早苗;Ping Luo
• 通讯作者: Ping Luo

Toyoshima H 他: "Effect of thiazolidinediones and metformin on LDL oxidation and aortic endothelium relaxation in diabetic GK rats"Am J Physiol Endocrinol Metab. 284(6). E1125-E1130 (2003)

Toyoshima H 等人：“噻唑烷二酮类和二甲双胍对糖尿病 GK 大鼠中 LDL 氧化和主动脉内皮松弛的影响”Am J Physiol Endocrinol Metab 284(6)。