Overexpression of rck/p54, a DEAD box protein, in human colorectal tumours

Nakagawa, Yoshihito; Morikawa, Hiroshi; Hirata, Ichiro; Shiozaki, Michiaki; Matsumoto, Akio; Maemura, Kentaro; Nishikawa, Takeshi; Niki, Masami; Tanigawa, Nobuhiko; Ikegami, Masachika; Katsu, Ken‐ichi; Akao, Yukihiro

doi:10.1038/sj.bjc.6690441

Cited by 71 publications

(70 citation statements)

References 8 publications

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“…Similarly, other DEAD box RNA helicases appear to be involved in tumor development. For instance, Rck/p54 is overexpressed in neuroblastoma, glioblastoma, rhabdomyosarcoma and lung cancer cells as well as in colorectal tumors (Akao et al, 1995;Nakagawa et al, 1999). Further, the DDX1 RNA helicase gene is often coamplified with N-myc in retinoblastomas and neuroblastomas and its co-amplification correlates with a poorer prognosis (Godbout and Squire, 1993;Squire et al, 1995;George et al, 1996).…”

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confidence: 99%

Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300

2003

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p68 RNA helicase has been implicated in a variety of processes, including rearrangement of RNA secondary structures, RNA splicing, gene transcription and tumor development, yet its mechanisms of action are not well understood. In this study, we show that p68 is predominantly localized to the cell nucleus, where it partially colocalizes with the transcriptional coactivator p300. Accordingly, p68 and p300, or the paralogous CREBbinding protein (CBP), coimmunoprecipitate. Similarly, p68 and RNA polymerase II (Pol II) are able to interact in vivo. GST pull-down assays confirmed these interactions in vitro, demonstrating that p68 can interact with several domains of CBP, while CBP/p300 bind to amino acids 176-388 of p68 and RNA Pol II binds to the N-terminal 80 amino acids of p68. Furthermore, p68 stimulates transcription mediated by the C-terminal transactivation domain of CBP. p68 is also able to stimulate TPA oncogene responsive unit (TORU) promoter activity, and p300 acts in synergy with p68. On the other hand, suppression of CBP/p300 function by the adenoviral protein E1A abolishes TORU promoter activation by p68. Altogether, our results suggest the existence of a multiprotein complex in which p68 RNA helicase, CBP/p300 and RNA Pol II jointly promote gene expression.

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confidence: 99%

Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300

2003

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“…So far, we have consistently reported data showing that high expression of rck/p54, a human DEAD-box/RNA unwindase, is associated with malignant transformation, especially by contributing to enhancement of potentiality for carcinogenesis by the deregulation of translation initiation control (12,14,(17)(18)(19)25). In the present study, we demonstrated that rck/p54 plays a role in the maintenance of cell growth probably by modulating the expression of genes involved in cell proliferation at the translation-initiation step, which is in line with the facts that rck/p54 has been verified as an RNA unwindase (14), its homologues have been reported to be associated with translational control (15,24,25) and, in the current study, rck/ p54 interacted with eIF4E.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we reported that rck/p54 was highly expressed in the majority of malignant cell lines and human colorectal tumors and HCV-related hepatocellular tumors (12,17,18). Also, high expression of rck/p54 frequently accompanied the c-myc overexpression seen in colon tumor cells; and evidence was obtained by the use of rck/p54-overexpressing SW480 cells, supporting the contribution of rck/p54 to the stabilization of c-myc mRNA and efficiency of c-myc translation (19).…”

Section: Introductionmentioning

confidence: 99%

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

Akao¹,

Matsumoto²,

Ohguchi³

et al. 2006

Int J Oncol

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Abstract. 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 translationinitiation control of the genes involved in the cell proliferation, which is a newly defined mechanism leading to carcinogenesis.

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“…Consistent with their essential biological roles, inactivation of helicases has been implicated in human genetic disorders such as xeroderma pigmentosum (Weeda et al, 1990), trichothiodystrophy (Broughton et al, 1994), Bloom syndrome (Ellis et al, 1995), Werner syndrome (Yu et al, 1996), and Rothmund Thomson syndrome (Kitao et al, 1999). On the other hand, over-expression of rck/ p54, a protein belonging to the DEAD box protein/ RNA family of helicases, is seen in B-cell lymphomas with t(11 ; 14)(q23 ; q32), and also in 50% of colorectal adenocarcinomas (Seto et al, 1995;Nakagawa et al, 1999). In addition, the DEAD box gene DDX1, encoding a putative RNA helicase, is co-amplified with N-myc in some retinoblastomas and neuroblastomas (Godbout et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Isolation of HELAD1, a novel human helicase gene up-regulated in colorectal carcinomas

et al. 2002

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To investigate the mechanisms of colorectal carcinogenesis, we searched for genes regulated by adenomatous polyposis coli gene product (APC) and identified a novel gene, termed HELAD1 (helicase, APC down-regulated 1). A recombinant polypeptide representing the ATPases associated with cellular activities (AAA) domain of the HELAD1 product showed 3' to 5' helicase activity and exonuclease activity in vitro. HELAD1 was abundantly expressed in 16 of 20 colon cancers examined but hardly detectable in corresponding non-cancerous mucosae. Treatment of colon-cancer cells with antisense oligonucleotides suppressed its expression and induced apoptosis. These data revealed an importance of HELAD1 in colorectal carcinogenesis and suggest that suppression of HELAD1 may be a promising therapeutic strategy.

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Overexpression of rck/p54, a DEAD box protein, in human colorectal tumours

Cited by 71 publications

References 8 publications

Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300

Synergism between p68 RNA helicase and the transcriptional coactivators CBP and p300

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

Isolation of HELAD1, a novel human helicase gene up-regulated in colorectal carcinomas

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