Promising targets for cancer drugs are translation initiation factors. mRNA translation is regulated in many cancers via a combination of protein overexpression and defects in the pathways that signal the translation machinery. Previously, we reported evidence that human RNA structure-modifying helicase 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 the maintenance of growth in cancer 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 knockdown of rck/p54 by using siRNA of RCK induced cell growth inhibition through cell cycle arrest at the S phase in HeLa cells. 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 5cap-structure and to be a rate-limiting factor in the initiation of translation. On the other hand, by use of cell and cell free systems we found that rck/p54 acts as a translation repressor of mRNAs such those of as c-myc and hepatitis C virus, which have an internal ribosomal entry site structure. The results of our recent study indicated that rck/p54 contributes to the suppression of the expression of let-7 which targets RAS. These data altogether suggest that rck/p54 positively affects cell growth probably by playing a role in the selection and quantity control of mRNAs at the translational level, leading to the fidelity of desirable gene expression for cell proliferation in cancer cells, which is a newly defined mechanism leading to carcinogenesis.
Keywords: DEAD-box RNA helicase, rck/p54, let-7, cancer development, overexpression
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