Akao Yukihiro, Matsumoto Kenji, Ohguchi Kenji, Nakagawa Yoshihito, Yoshida Hitoshi
Gifu International Institute of Biotechnology, Kakamigahara, Gifu 504-0838, Japan.
Int J Oncol. 2006 Jul;29(1):41-8.
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 the 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 induced cell growth inhibition through cell cycle arrest at S phase. Immunoprecipitation using anti-rck/p54 antibody in 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.
要理解癌细胞中基因表达的调控，需要明确与稳态正常细胞相比，RNA代谢的分子和细胞基础。此前，我们报道了证据表明，人类RNA结构修饰解旋酶rck/p54（DEAD-box家族成员）在大多数测试的恶性细胞系中高表达，且这种表达与恶性转化有关。在此，我们表明rck/p54可能通过在培养细胞的翻译水平上调节基因表达来正向影响细胞生长。在外部刺激诱导的细胞生长和分化过程中，rck/p54的表达水平在细胞增殖期间上调，在分化期间下调。通过RNAi使HeLa细胞中的rck/p54下调，导致细胞周期停滞在S期，从而抑制细胞生长。在HeLa细胞中使用抗rck/p54抗体进行免疫沉淀，证明rck/p54与eIF4E共沉淀，eIF4E众所周知可与5'帽结构结合，从而启动翻译。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。
