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

要了解癌细胞中基因表达的控制，需要确定与稳定状态的正常细胞相比，RNA代谢的分子和细胞基础。此前，我们曾报道过有证据表明，DEAD-BOX家族的人RNA结构修饰解旋酶RCK/P54在大多数被测试的恶性细胞系中都高表达，并且这种表达与恶性转化有关。在这里，我们表明RCK/p54对细胞生长有积极的影响，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分化过程中，rck/p54的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细胞中RCK/p54的表达，使细胞周期停滞于S期，从而抑制细胞生长。抗rck/p54抗体与HeLa细胞的免疫共沉淀表明，rck/p54与eIF4E共沉淀，eIF4E结合在5‘端的帽结构上，导致翻译的启动。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启动控制而促进细胞生长，这是一种新定义的致癌机制。

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.