Molecular cloning and functional analysis of a novel oncogene, cancer-upregulated gene 2 (CUG2)

Lee, Soojin; Gang, Jingu; Jeon, Sun Bok; Choo, Seung Ho; Lee, Bogman; Kim, Young Gun; Lee, Yang Soon; Jung, Jin‐Young; Song, Si Young; Koh, Sang Seok

doi:10.1016/j.bbrc.2007.06.102

Cited by 48 publications

(60 citation statements)

References 15 publications

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“…In a previous study, CUG2 expression was shown to exhibit anchorage-independent growth on soft agar and metastatic features in a cell invasion and migration assay, 1 which is comparable to Ras oncogenecity; however, the tumorigenic mechanism has not yet been revealed. Other studies also reported that the activity of Src kinase was elevated in a variety of human cancers and has been linked with the progression and metastasis of cancer through the VEGF, Akt and ERK pathways.…”

Section: Discussionmentioning

confidence: 97%

“…As we recently identified a novel tumor-associated gene, CUG2, that is commonly activated in various cancers and exhibits high transforming activity, 1 we examined whether reovirus can be used to induce cytolysis in CUG2-expressing cells and thus be used as a potential anticancer drug. To answer this question, we first used a nonpermissive NIH3T3 cell line expressing either the vector only (NIH-Vec) or the vector containing the CUG2 gene (NIH-CUG2).…”

Section: Cug2 Renders Reoviral Replication Leading To Cell Death In mentioning

confidence: 99%

“…We found tumor formation (20 mm 3 ) at the injection site of all the mice transplanted with NIH-CUG2 cells within 4 weeks. 1 When the mice were subsequently administered with UV-inactivated reovirus, tumors developed more aggressively at the site of injection for another 4 weeks (Figure 2a). However, when the mice bearing NIH-CUG2 tumor cells were treated with live reovirus, the tumor size shrunk.…”

Section: Cug2 Renders Reoviral Replication Leading To Cell Death In mentioning

confidence: 99%

“…Finally, CUG2 has been shown to posses an oncogenic effect in a transplanted model using NIH3T3 cells expressing CUG2, which was similar to Ras. 1 The human reovirus is a ubiquitous, nonenveloped virus with 10 segments of double-stranded RNA. 2,3 The virus infection is usually restricted to the upper respiratory and gastrointestinal tracts and is often asymptomatic.…”

Section: Introductionmentioning

confidence: 99%

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CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway

Park

I-R

et al. 2010

Cancer Gene Ther

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As we have recently found a novel oncogene, the cancer-upregulated gene 2 (CUG2), which was elevated in a variety of tumor tissues such as the ovary, liver, lung and pancreas, we examined whether reovirus could efficiently induce cytolysis in cancer cells expressing CUG2 and thus be used as a potential cancer therapeutic agent. In this study, we describe experiments in which we use reovirus to treat NIH3T3 cells stably expressing either CUG2 (NIH-CUG2) or vector only (NIH-Vec). NIH-CUG2 cells readily support reoviral proliferation and undergo apoptosis, whereas NIH-Vec cells are highly resistant to reoviral infection and virusinduced apoptosis. This notable result may be explained by the observation that CUG2 expression inhibits PKR activation, leading to reoviral proliferation in nonpermissive NIH3T3 cells. Furthermore, reovirus infection results in almost complete regression of tumorgenic NIH-CUG2 cells in transplanted nude mice. As we found that CUG2 enhances activation of MAPK (ERK, JNK and p38), Src kinase and Ras, we examined whether CUG2 confers reoviral replication independent of the Ras or p38 MAPK signaling pathway. From these experiments we found that either inhibition of p38 MAPK or Ras blocks reoviral proliferation even in the presence of CUG2 but inhibition of ERK, JNK and Src kinase does not, indicating that activation of p38 MAPK and Ras has critical roles in reoviral replication in CUG2-expressing tumor cells. Accordingly, we propose that reovirus can be useful in the treatment of transformed cells expressing CUG2, which is commonly detected in various tumor tissues.

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Section: Discussionmentioning

confidence: 97%

Section: Cug2 Renders Reoviral Replication Leading To Cell Death In mentioning

confidence: 99%

Section: Cug2 Renders Reoviral Replication Leading To Cell Death In mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway

Park

I-R

et al. 2010

Cancer Gene Ther

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“…CUG2 was mapped to chromosome 6q22.32; it spans ~8.5 kb with a three-exon structure and encodes an 88-amino-acid polypeptide (1). Further study revealed that CUG2 is a new centromere component that is required for proper kinetochore function during cell division (2).…”

Section: Introductionmentioning

confidence: 99%

Suppression of autophagic genes sensitizes CUG2-overexpressing A549 human lung cancer cells to oncolytic vesicular stomatitis virus-induced apoptosis

Malilas¹,

Koh²,

Lee³

et al. 2014

International Journal of Oncology

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Abstract. We showed in our previous study that cancer upregulated gene (CUG) 2, a novel oncogene, confers resistance to infection of oncolytic vesicular stomatitis virus (VSV) by activating Stat1-mediated signal transduction. Since many studies have reported that autophagy is involved in virus replication, we investigated whether autophagy also plays a role in the antiviral activity in A549 cells overexpressing CUG2 (A549-CUG2). We suppressed Atg5 or Beclin 1 expression using siRNA and examined its effect on the susceptibility of cells to infection by oncolytic VSV. We found that A549-CUG2 cells treated with Atg5 or Beclin 1 siRNA became susceptible to VSV infection, whereas A549-CUG2 cells treated with control siRNA were resistant. This result suggests that autophagy is involved in the antiviral response of A549-CUG2 cells. Further investigation revealed that autophagy impairment enhanced the generation of reactive oxygen species (ROS), which resulted in inactivation of S6 kinase. Under these conditions, the levels of ISG15 transcript and protein decreased, which conferred on A549-CUG2 cell susceptibility to VSV infection. Finally, we found that overloading of H 2 O 2 sensitized control A549-CUG2 cells to VSV-induced apoptosis. Taken together, these results indicate that autophagy impairment induces excessive ROS formation, which decreases S6 kinase activity and ISG15 expression, ultimately rendering the A549-CUG2 cells susceptible to VSV infection. We propose that autophagy impairment is a potential strategy for successful VSV virotherapy of CUG2-overexpressing tumors.

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Centromere protein W interacts with beta‐transducin repeat‐containing protein 1 and modulates its subcellular localization

2016

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Beta-transducin repeat-containing protein 1 (b-TrCP1) is a substrate-recognition module of SCF b-TrCP1 ubiquitin ligases and its subcellular distribution is known to be critical for target specificity. Heterogeneous nuclear ribonucleoprotein (hnRNP) U, an abundant nuclear protein, is known to be a unique regulator of b-TrCP1 shuttling between the cytoplasm and the nucleus. In this study, we report that centromere protein W (CENP-W), which is frequently overexpressed in a variety of human cancers, may also contribute to b-TrCP1 shuttling. Although hnRNP U and CENP-W can interact with b-TrCP1 and transport it independently, these proteins do not compete for b-TrCP1 binding, but rather cooperate to form a stable shuttling complex. Intriguingly, we found that overexpression of CENP-W leads to accumulation of b-TrCP1 in the nucleus. Thus, we propose that CENP-W may function as a booster of b-TrCP1 nuclear import to increase the oncogenicity of b-TrCP1.

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Molecular cloning and functional analysis of a novel oncogene, cancer-upregulated gene 2 (CUG2)

Cited by 48 publications

References 15 publications

CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway

CUG2, a novel oncogene confers reoviral replication through Ras and p38 signaling pathway

Suppression of autophagic genes sensitizes CUG2-overexpressing A549 human lung cancer cells to oncolytic vesicular stomatitis virus-induced apoptosis

Centromere protein W interacts with beta‐transducin repeat‐containing protein 1 and modulates its subcellular localization

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