Anchorage independent cell cycle start

贴壁独立细胞周期启动

• 批准号: 12670107
• 负责人: JINNO Shigeki
• 金额: $ 2.11万
• 依托单位: The University of Tokyo,
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670107/
• 关键词: Cell cycle; Anchorage; NRK; E2F; Cdk; Cdc6; 足場非依存性増殖; cdc6; G1; サイクリンD3; 癌化; cdk6

Fibroblasts need anchorage to extracellular matrix to transit from G1 to S phase, but no longer after oncogenic transformation. We report that Cdc6 protein essential for the activation of replication origins requires anchorage or oncogenic stimulation for its execution. Upon anchorage loss, Cdc6 expression is shut of both transcriptionally and post-transcriptionally in a rat fibroblast despite enforced activation of E2F-dependent promoters. However, stimulation of this cell with oncogenic growth factors suppresses this shutoff and concurrently activates Cdk2 and Cdk6/4, thereby overriding the anchorage requirement for the G1-S transition and consequently enabling cells to perform anchorage-independent S phase entry. Analysis with enforced expression of Cdc6 indicates that the G1 cyclin-dependent kinases and Cdc6 constitute major cell cycle targets for the restriction of the G1-S transition by anchorage loss.

成纤维细胞需要锚定到细胞外基质从G1期过渡到S期，但不再致癌转化后。我们报告说，Cdc 6蛋白的复制起点的激活必不可少的需要锚定或致癌刺激其执行。锚定损失后，Cdc 6的表达是关闭的转录和转录后在大鼠成纤维细胞，尽管强制激活E2 F依赖性启动子。然而，刺激这种细胞与致癌生长因子抑制这种关闭，并同时激活Cdk 2和Cdk 6/4，从而推翻了G1-S转换的锚定要求，从而使细胞进行锚定独立的S期进入。与Cdc 6的强制表达的分析表明，G1期细胞周期蛋白依赖性激酶和Cdc 6构成的G1-S转换的限制锚定损失的主要细胞周期的目标。

项目成果

Lin, J., Jinno, S., Okayama, H.: "Cdk6-cyclin D3 complex evades inhibition by inhibitor proteins and uniquely controls cell's proliferation competence"Oncogene. 20. 2000-2009 (2001)

Lin, J.、Jinno, S.、Okayama, H.：“Cdk6-细胞周期蛋白 D3 复合物逃避抑制剂蛋白的抑制，并独特地控制细胞的增殖能力”癌基因。

Hiroi, N., Ito, T., Yamamoto. H., Ochiya, T., Jinno, S., and Okayama, H.: "Mammalian Rcd1 is a novel transcriptional cofactor that mediates retinoic acid-induced cell differentiation"The EMBO Journal. 21. 5235-5244 (2002)

广井，N.，伊藤，T.，山本。

Isobe, H., Tomita, N., Jinno, S., Okayama, H., Nakamura, E.: "Synthesis and transfection capability of multi-fanctionalized fullerene polyamine"Chemistry Letters. 2001. 1213-1215 (2001)

Isobe, H.、Tomita, N.、Jinno, S.、Okayama, H.、Nakamura, E.：“多官能富勒烯多胺的合成和转染能力”化学快报。

Jinno, S., Lin, J., Yageta, M., Okayama, H.: "Oncogenic cell cycle start control"Mutatin Reseach. 477. 23-29 (2001)

Jinno, S.、Lin, J.、Yageta, M.、Okayama, H.：“致癌细胞周期启动控制”突变研究。

Jinno, S., Yageta, M., Nagata, A., Okayama, H.: "Cdc6 requeres anchorage for its expression"Oncogene. 21(in press). (2002)

Jinno, S.、Yageta, M.、Nagata, A.、Okayama, H.：“Cdc6 需要锚定来表达”癌基因。