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

Akao, Yukihiro; Matsumoto, Kenji; Ohguchi, Ken-ichi; Nakagawa, Yoshihito; Yoshida, Hitoshi

doi:10.3892/ijo.29.1.41

Cited by 20 publications

(26 citation statements)

References 23 publications

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“…The overexpression of RCK/p54 gene has been found in many malignancies, such as colorectal cancer, cervical carcinoma, hepatocarcinoma. 5,13,14 In this study, we want to explore whether RCK/p54 plays a role in maintaining the malignant phenotypes and becomes a therapeutic target for the treatment of human colorectal cancers. RNA interference (RNAi) is a recently discovered posttranscriptional gene silencing mechanism, which can specifically silence gene therapy.…”

Section: Resultsmentioning

confidence: 99%

“…Our results were also consistent with Akao Y's research in human cervical carcinoma cells. 13 Apoptosis induction by RCK/p54-shRNA1 in LoVo cells. To determine whether the proliferation inhibition of LoVo cells by RCK/p54shRNA1 was induced by cell apoptosis, we performed FCM and TUNEL assays to measure the levels of apoptosis in LoVo cells expressing RCK/p54shRNA.…”

Section: Resultsmentioning

confidence: 99%

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Knockdown of RCK/p54 expression by RNAi inhibits proliferation of human colorectal cancer cells in vitro and in vivo

Lin¹,

Wang²,

Shen³

et al. 2008

Cancer Biology & Therapy

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Colorectal cancer is the third most common cancer in both men and women around the world. Although much progress of the mechanism of colorectal carcinogenesis has been made, the studies centering on the mechanisms of tumorigenesis are much needed to be further exploited. The overexpression of RCK/p54 gene, a member of the DEAD box protein/RNA helicase family, has been found in this malignancy. Roles of RCK in the development of colon cancer, however, are unknown. In this report, we explored whether RCK/p54 plays a role in maintaining the malignant phenotype and functions in the canonical Wnt signaling pathway of colorectal cancer cells harboring an APC mutation. The ectopic overexpression of RCK/p54 gene in colorectal cancer cells by transfection with RCK/p54 cDNA could lead to a significant increase of Tcf transcriptional activity and expression levels of Wnt target genes. By RNAi assay, we also observed that the Tcf transcriptional activity in LoVo-shRNA cells was significantly decreased by approximately 61.3%, while the mRNA and protein expression levels of Wnt target genes were also obviously decreased. Furthermore, the anti-tumour effects and its possible mechanisms of actions in LoVo cells elicited by a decrease in the level of RCK/ p54 by RNAi were examined. Results showed that RCK/p54 downregulation could significantly reduce the viability of LoVo cells, increased cell number of S phase, led to cell apoptosis induction, and inhibited tumor growth in nude mice. Taken together, RCK/ p54 might be a determinant of colorectal cancer proliferation by activating the canonical Wnt pathway and RCK/p54-shRNA might be a potential strategy for colorectal cancer gene therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Knockdown of RCK/p54 expression by RNAi inhibits proliferation of human colorectal cancer cells in vitro and in vivo

Lin¹,

Wang²,

Shen³

et al. 2008

Cancer Biology & Therapy

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“…Can both promote and repress translation initiation: associates with P-bodies, ATP hydrolysis allows release from P-bodies and translation initation [32][33][34][35][36][37] 58,65 Developmental roles in many species [57][58][59][60][61][62] Overexpression in several cancers [53][54][55][56] Stimulation of cell cycle progression and proliferation [70][71][72][73][74] Cell cycle progression/proliferation Dhh1p important for recovery from DNA damageinduced G1/S cell cycle arrest in yeast DDX6 required for S-phase progression and cell viability in HeLa and LoVo cells, 73,74 and proliferation in xenograft models 74 (siRNA studies)…”

Section: Translationmentioning

confidence: 99%

“…Several studies, with both the human DDX6 and the yeast Dhh1p, have indicated that this protein acts as a positive regulator of cell cycle progression: Dhh1p has been shown to be important for recovery from DNA-damage-dependent G1/S cell cycle arrest, 72 while two separate studies demonstrated that siRNA knockdown of DDX6 resulted in S-phase cell cycle arrest. 73,74 Furthermore, these studies showed that siRNA knockdown of DDX6 resulted in a reduction in cell viability, 73 as well as an increase in cell apoptosis and a reduction in their ability to form tumors in xenograft models. 74 Additionally, overexpression of DDX6 was shown to increase expression of the oncogene c-Myc, consistent with the idea that it would have a positive effect on cell proliferation.…”

mentioning

confidence: 99%

DEAD box RNA helicase functions in cancer

2013

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“…A second mechanism by which CNOT7 and CNOT8 contribute to cell proliferation may be by positively regulating the expression of genes required for cell proliferation, such as the DEAD-box RNA helicase DDX6/Rck/p54 (Akao et al, 2006). Interestingly, DDX6 is a homologue of yeast Dhh1, which interacts with the Ccr4 -Not complex (Coller et al, 2001;Maillet and Collart, 2002).…”

Section: Cnot7 and Cnot8 Are Important For Efficient Cell Proliferatimentioning

confidence: 99%

The Ccr4–Not Deadenylase Subunits CNOT7 and CNOT8 Have Overlapping Roles and Modulate Cell Proliferation

Aslam

Mittal

Koch

et al. 2009

MBoC

104

115

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Accurate gene expression requires the precise control of mRNA levels, which are determined by the relative rates of nuclear (pre-)mRNA synthesis and processing, and cytoplasmic mRNA turnover. A key step in mRNA degradation is the removal of the poly(A) tail, which involves several deadenylases including components of the Ccr4 -Not complex. Here, we focused on the role of the human paralogues CNOT7 (hCaf1/Caf1a) and CNOT8 (hPop2/Caf1b/Calif), which possess deadenylase activity mediated by DEDD nuclease domains. We show that efficient proliferation requires both subunits, although combined knockdown of CNOT7 and CNOT8 further reduces cell proliferation indicating partial redundancy between these proteins. Interestingly, the function of CNOT7 in cell proliferation partly depends on its catalytic activity. On the other hand, the interaction between CNOT7 and BTG2, a member of the antiproliferative BTG/Tob family involved in transcription and mRNA decay appears less important for proliferation of MCF7 cells, suggesting that CNOT7 does not function solely in conjunction with BTG2. Further analysis of gene expression profiles of CNOT7 and/or CNOT8 knockdown cells underscores the partial redundancy between these subunits and suggests that regulation of several genes, including repression of the antiproliferative genes MSMB and PMP22, by the Ccr4 -Not complex contributes to cell proliferation. INTRODUCTIONAccurate gene expression requires the precise control of mRNA levels that are determined by the relative rates of (pre-)mRNA synthesis and processing, and by mRNA turnover. Degradation of eukaryotic mRNA is initiated by the shortening and removal of the poly(A) tail by at least two different complexes containing distinct deadenylase subunits (Parker and Song, 2004;Garneau et al., 2007;Goldstrohm and Wickens, 2008). In both yeast and human cells, initial shortening of the poly(A) tail is carried out by Pan2, which forms a heterodimer with Pan3 (Brown et al., 1996;Boeck et al., 1998;Brown and Sachs, 1998;Uchida et al., 2004). Subsequent removal of poly(A) residues is achieved by Ccr4 -Not, a conserved complex, which contains about 10 subunits, including several deadenylase components (Tucker et al., 2001;Temme et al., 2004;Yamashita et al., 2005). The yeast Ccr4 protein and its human orthologues CNOT6 (hCcr4/Ccr4a) and CNOT6L (hCcr4-like/Ccr4b) contain an exonuclease/endonuclease/ phosphatase (EEP) domain that is responsible for the RNA nuclease activity (Dupressoir et al., 2001;Chen et al., 2002;Tucker et al., 2002;Morita et al., 2007). In addition, these proteins interact via leucine-rich motifs with yeast Caf1 (Pop2) or its human orthologues CNOT7 (hCaf1/Caf1a) and CNOT8 (hPop2/Caf1b/Calif), which contain RNA nuclease activities attributed to DEDD domains (Daugeron et al., 2001;Dupressoir et al., 2001;Clark et al., 2004;Viswanathan et al., 2004;Bianchin et al., 2005). The CNOT7 and CNOT8 proteins interact with members of the BTG/Tob family of antiproliferative proteins, which are implicated in mRNA turnover (Ezzeddine ...

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

Cited by 20 publications

References 23 publications

Knockdown of RCK/p54 expression by RNAi inhibits proliferation of human colorectal cancer cells in vitro and in vivo

Knockdown of RCK/p54 expression by RNAi inhibits proliferation of human colorectal cancer cells in vitro and in vivo

DEAD box RNA helicase functions in cancer

The Ccr4–Not Deadenylase Subunits CNOT7 and CNOT8 Have Overlapping Roles and Modulate Cell Proliferation

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