Human DEAD-box/RNA helicase rck/p54 contributes to maintenance of cell growth by affecting cell cycle in cultured cells

人 DEAD-box/RNA 解旋酶 rck/p54 通过影响培养细胞的细胞周期来维持细胞生长

• 批准号: 16590334
• 负责人: AKAO Yukihiro
• 金额: $ 2.3万
• 依托单位: Gifu International Institute of Biotechnology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590334/
• 关键词: translation initiation; degradation of mRNAs; rck; p54; cell proliferation; DAED-box RNA helicase; cell cycle; carcinogenesis; genes associated with chromosome translocation; RNA分解; DEAD-bex RNAヘリカーゼ; eIF4E; DEAD-box; RNAヘリカーゼ

Understanding the control of gene expression in cancer cells requires defining the molecular and cellular basis of RNA metabolism compared with that in steady-state normal cells. Previously, we reported evidence that human RNA structure-modifying unwindase rck/p54, a member of DEAD-box family, was highly expressed in most of the malignant cell lines tested and that this expression was linked to malignant transformation. Here, we show that rck/p54 positively affects cell growth, probably by modulating the gene expression at the translational level in cultured cells. In cell growth and differentiation induced by external stimuli, the level of rck/p54 expression was up-regulated during cell proliferation and down-regulated during differentiation. The down-regulation of rck/p54 in HeLa cells by RNAi inhibited cell growth through cell cycle arrest at S phase. Immunoprecipitation using anti-rck/p54 antibody and HeLa cells demonstrated the co-precipitation of rck/p54 with eIF4E, which is well known to bind to the 5'cap-structure, resulting in initiation of translation. These data suggest that rck/p54 contributes to cell growth possibly by modulating translation-initiation control of the genes involved in the cell proliferation, which is a newly defined mechanism leading to carcinogenesis.

理解癌细胞中基因表达的控制需要定义RNA代谢的分子和细胞基础，与稳态正常细胞相比。以前，我们报道的证据表明，人RNA结构修饰解链酶rck/p54，死亡盒家族的成员，在大多数恶性肿瘤细胞系中高度表达，这种表达与恶性转化。在这里，我们表明，rck/p54积极影响细胞生长，可能是通过在培养细胞的翻译水平上调节基因表达。在外界刺激诱导的细胞生长和分化过程中，rck/p54表达水平在细胞增殖过程中上调，在分化过程中下调。RNAi下调HeLa细胞rck/p54基因表达可使细胞周期阻滞于S期，从而抑制HeLa细胞的生长。使用抗rck/p54抗体和HeLa细胞的免疫沉淀证实了rck/p54与eIF 4 E的共沉淀，众所周知eIF 4 E结合5 '帽结构，导致翻译的起始。这些数据表明，rck/p54可能通过调节参与细胞增殖的基因的翻译起始控制来促进细胞生长，这是一种新定义的致癌机制。

项目成果

Human DEAD-box/RNA helicase rck/p54 contributes to maintenance of cell growth by affecting cell cycle in cultured cells.

人 DEAD-box/RNA 解旋酶 rck/p54 通过影响培养细胞的细胞周期来维持细胞生长。

• 发表时间: 2006
• 期刊: Int J Oncol (in press)
• 作者: Akao Y;Matsumoto K;Ohguchi K;Nakagawa Y.
• 通讯作者: Nakagawa Y.

Crystallization and X-ray analysis of the N-terminal core domain of a tumour-associated human DEAD-box RNA helicase, rck/p54.

肿瘤相关人 DEAD-box RNA 解旋酶 rck/p54 N 端核心结构域的结晶和 X 射线分析。

• 发表时间: 2004
• 期刊: Acta Crystallographica D60
• 作者: Matsui;T.;et al.
• 通讯作者: et al.

Expression of the DEAD-box/RNA helicase rck/p54 in mouse tissues : Implications for heterogeneous protein expression

DEAD-box/RNA 解旋酶 rck/p54 在小鼠组织中的表达：对异质蛋白表达的影响

• 发表时间: 2006
• 期刊: J Histochem Cytochem (In press)
• 作者: Akao Y;Nakagawa Y.
• 通讯作者: Nakagawa Y.

Expression of the DEAD-box/RNA Helicase rck/p54 in Mouse Tissues : Implications for Heterogeneous Protein Expression.

DEAD-box/RNA 解旋酶 rck/p54 在小鼠组织中的表达：对异质蛋白表达的影响。

• 发表时间: 2006
• 期刊: J Histochem Cytochem (in press)
• 作者: Akao Y;Nakagawa Y.
• 通讯作者: Nakagawa Y.

Structural insight of human DEAD-box protein rck/p54 into its substrate recognition with conformational changes

• DOI: 10.1111/j.1365-2443.2006.00951.x
• 发表时间: 2006-04-01
• 期刊: GENES TO CELLS
• 影响因子: 2.1
• 作者: Matsui, T;Hogetsu, K;Tanaka, N
• 通讯作者: Tanaka, N