Human DEAD-box/RNA unwindase rck/p54 contributes to maintenance of cell growth by affecting cell cycle in cultured cells.
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.
Akao
Yukihiro
Y
Gifu International Institute of Biotechnology, Kakamigahara, Gifu 504-0838, Japan. yakao@giib.or.jp
Matsumoto
Kenji
K
Ohguchi
Kenji
K
Nakagawa
Yoshihito
Y
Yoshida
Hitoshi
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D020298:U937 Cells
D039561:Eukaryotic Initiation Factor-4E; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C094683:DDX6 protein, human; D053487:DEAD-box RNA Helicases