<i>Retracted</i>: Overexpression of Aurora A by loss of CHFR gene expression increases the growth and survival of HTLV‐1‐infected T cells through enhanced NF‐κB activity

Tomita, Masaru; Toyota, Minoru; Ishikawa, Chie; Nakazato, Tetsuro; Okudaira, Taeko; Matsuda, Takehiro; Uchihara, Jun Nosuke; Taira, Naoya; Ohshiro, Kazuiku; Senba, Masachika; Tanaka, Yuetsu; Ohshima, Koichi; Saya, Hideyuki; Tokino, Takashi; Mori, Nozomu

doi:10.1002/ijc.24257

Cited by 14 publications

(20 citation statements)

References 44 publications

(65 reference statements)

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“…15 We reported previously that a pan-Aurora kinase inhibitor, which inhibits both Aurora A and Aurora B kinases, suppresses cell growth of HTLV-1-infected T-cell lines and primary ATL cells by inducing apoptosis through inhibition of nuclear factor-kappa B (NF-jB) activity. 16 In our study, we used AZD1152-HQPA in vitro to evaluate the effects of specific inhibition of Aurora B in HTLV-1-infected T-cell lines.…”

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confidence: 99%

Retracted: Aurora kinase inhibitor AZD1152 negatively affects the growth and survival of HTLV‐1‐infected T lymphocytes in vitro

Tomita

Tanaka

Mori

2010

Intl Journal of Cancer

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Aurora kinases play an essential role in regulating mitosis and cell division. Inhibition of Aurora kinases results in suppression of cell division, phosphorylation of histone H3 and induction of apoptosis in many cell types. These characteristics have prompted the testing of Aurora kinase inhibitors as chemotherapeutic agents. In our study, we report the in vitro activities of AZD1152, a selective inhibitor of Aurora B kinase in human T-cell leukemia virus type 1 (HTLV-1), the causative agent of adult T-cell leukemia (ATL), -infected T-cell lines. Overexpression of Aurora B was noted in HTLV-1-infected T-cell lines compared to HTLV-1-uninfected T-cell lines. AZD1152 reduced the viability of HTLV-1-infected T-cell lines within 24 hr but did not affect that of -uninfected T-cell lines. Although AZD1152 inhibited phosphorylation of histone H3 on Ser10 in both HTLV-1-infected and -uninfected T-cell lines, it induced polyploidy only in HTLV-1-uninfected T-cell lines. AZD1152 induced early apoptosis of HTLV-1-infected T-cells without induction of polyploidy. We have reported previously that a panAurora kinase inhibitor induced apoptosis through inhibition of NF-jB signaling activity in HTLV-1-infected T-cell lines. In contrast, AZD1152 did not affect NF-jB activity in these cells. It induced p53 and p21 expression in HTLV-1-infected but not in HTLV-1-uninfected T-cell lines, suggesting that activation of p53-dependent postmitotic checkpoint might prevent polyploidy in HTLV-1-infected T-cells. Our results suggest that specific inhibition of Aurora B kinase is a potentially useful therapeutic strategy in the treatment of ATL and that further in vivo exploration is warranted.

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confidence: 99%

Retracted: Aurora kinase inhibitor AZD1152 negatively affects the growth and survival of HTLV‐1‐infected T lymphocytes in vitro

Tomita

Tanaka

Mori

2010

Intl Journal of Cancer

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“…However, no evidence showing CHFR ubiquitination of Aurora A directly leading to instability was demonstrated (140). Nonetheless, several other studies showed that downregulation or loss of CHFR in cells is closely associated with elevated Aurora A expression (89,98,125). However, CHFR overexpression in HCT116 cells did not destabilize Aurora A (116).…”

Section: Molecular Characterization Of Chfrmentioning

confidence: 98%

Safeguarding Entry into Mitosis: the Antephase Checkpoint

Chin

Yeong

2010

Molecular and Cellular Biology

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Maintenance of genomic stability is needed for cells to survive many rounds of division throughout their lifetime. Key to the proper inheritance of intact genome is the tight temporal and spatial coordination of cell cycle events. Moreover, checkpoints are present that function to monitor the proper execution of cell cycle processes. For instance, the DNA damage and spindle assembly checkpoints ensure genomic integrity by delaying cell cycle progression in the presence of DNA or spindle damage, respectively. A checkpoint that has recently been gaining attention is the antephase checkpoint that acts to prevent cells from entering mitosis in response to a range of stress agents. We review here what is known about the pathway that monitors the status of the cells at the brink of entry into mitosis when cells are exposed to insults that threaten the proper inheritance of chromosomes. We highlight issues which are unresolved in terms of our understanding of the antephase checkpoint and provide some perspectives on what lies ahead in the understanding of how the checkpoint functions.Segregation of sister chromosomes during the metaphaseto-anaphase transition is a dramatic event that results in the inheritance of a complete set of chromosomes by each daughter cell undergoing cell division. This process, which occurs during mitosis, requires the temporal and spatial coordination of a myriad of proteins. As many excellent reviews on the process of chromosome segregation have been published (9,37,84,97,136), we give here an overview of the process.In essence, duplicated chromosomes are condensed and then lined up at the metaphase plate, where the sister chromatids are subsequently pulled apart by microtubules attached to the kinetochores. The duplicated chromosomes are condensed by condensin I and II complexes that function to pack interphase chromatin so that it can then be neatly divided into daughter cells (6, 48, 50) (see below). Yet other protein complexes essential for ensuring genomic integrity during nuclear separation are the cohesins which maintain cohesion between sister chromatids (17, 85). The cohesins are loaded onto the duplicated chromosomes toward the end of mitosis in the preceding round of cell division or in late G 1 /early S phase in the new round of cell division (9,90,111,130). The presence of the cohesins helps keep the sister chromatids together until the kinetochores are correctly attached to spindle microtubules emanating from both microtubule-organizing centers (i.e., the spindle pole bodies in Saccharomyces cerevisiae or the centrosomes in higher eukaryotes) in a process known as bi-orientation (122). Upon proper attachment of the mitotic spindles to the kinetochores, the sister chromatids separate as cohesins are destroyed through proteolysis by separase, a CD clan protease (129). Chromosome separation occurs as the spindle microtubules pull the chromosomes toward opposite ends of the dividing cells. This process of chromosome segregation is highly complex and requires tight regulation in ord...

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“…Aurora A is overexpressed in HTLV-1-infected and ATLL cells. siRNA knockdown experiments and chemical inhibition of Aurora A has been reported to lead to growth suppression in HTLV-1-infected cell [65] . The ubiquitin ligase CHFR regulates the turnover of Aurora A, and in infected cells CHFR level is reduced by methylation and subsequent silencing of its promoter [65] .…”

Section: Cell Cyclementioning

confidence: 99%

“…siRNA knockdown experiments and chemical inhibition of Aurora A has been reported to lead to growth suppression in HTLV-1-infected cell [65] . The ubiquitin ligase CHFR regulates the turnover of Aurora A, and in infected cells CHFR level is reduced by methylation and subsequent silencing of its promoter [65] . Aurora B is overexpressed in HTLV-1-infected cells and its specific inhibition induces apoptosis only in HTLV-1-infected cells compared to non-infected, through overexpression of p21/Waf1 and p53 [66] .…”

Section: Cell Cyclementioning

confidence: 99%

Human T-lymphotropic virus proteins and post-translational modification pathways

Bidoia

2012

WJV

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Cell life from the cell cycle to the signaling transduction and response to stimuli is finely tuned by protein post-translational modifications (PTMs). PTMs alter the conformation, the stability, the localization, and hence the pattern of interactions of the targeted protein. Cell pathways involve the activation of enzymes, like kinases, ligases and transferases, that, once activated, act on many proteins simultaneously, altering the state of the cell and triggering the processes they are involved in. Viruses enter a balanced system and hijack the cell, exploiting the potential of PTMs either to activate viral encoded proteins or to alter cellular pathways, with the ultimate consequence to perpetuate through their replication. Human T-lymphotropic virus type 1 (HTLV-1) is known to be highly oncogenic and associates with adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy/tropical spastic paraparesis and other inflammatory pathological conditions. HTLV-1 protein activity is controlled by PTMs and, in turn, viral activity is associated with the modulation of cellular pathways based on PTMs. More knowledge is acquired about the PTMs involved in the activation of its proteins, like Tax, Rex, p12, p13, p30, HTLV-I basic leucine zipper factor and Gag. However, more has to be understood at the biochemical level in order to counteract the associated fatal outcomes. This review will focus on known PTMs that directly modify HTLV-1 components and on enzymes whose activity is modulated by viral proteins.

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Retracted: Overexpression of Aurora A by loss of CHFR gene expression increases the growth and survival of HTLV‐1‐infected T cells through enhanced NF‐κB activity

Cited by 14 publications

References 44 publications

Retracted: Aurora kinase inhibitor AZD1152 negatively affects the growth and survival of HTLV‐1‐infected T lymphocytes in vitro

Retracted: Aurora kinase inhibitor AZD1152 negatively affects the growth and survival of HTLV‐1‐infected T lymphocytes in vitro

Safeguarding Entry into Mitosis: the Antephase Checkpoint

Human T-lymphotropic virus proteins and post-translational modification pathways

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