Up-regulation of β-catenin by a viral oncogene correlates with inhibition of the seven in absentia homolog 1 in B lymphoma cells

Jang, Kyung Lib; Shackelford, Julia; Seo, So Young; Pagano, Joseph S.

doi:10.1073/pnas.0504054102

Cited by 50 publications

(52 citation statements)

References 36 publications

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“…Importantly, this mechanism is GSK-3b-independent and, indeed (like NS5A), LMP1 and LiCl exhibited an additive effect on b-catenin transcriptional activity. Furthermore, LMP1 was able to activate a mutant b-catenin that was unable to be phosphorylated by GSK-3b (S37A) (Jang et al, 2005). It will be intriguing to determine whether NS5A also modulates the Siah-1 pathway of b-catenin regulation; current efforts in our laboratory are investigating this topic.…”

Section: Discussionmentioning

confidence: 99%

“…However, a more compelling explanation is suggested by the parallels between NS5A and the EBV latent membrane protein 1 (LMP1), which also activates b-catenin (Shackelford et al, 2003). LMP1 has been shown to inhibit an alternative pathway of b-catenin ubiquitination, involving the Siah-1 (seven in absentia homologue 1) ubiquitin ligase (Jang et al, 2005). Importantly, this mechanism is GSK-3b-independent and, indeed (like NS5A), LMP1 and LiCl exhibited an additive effect on b-catenin transcriptional activity.…”

Section: Discussionmentioning

confidence: 99%

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Hepatitis C virus NS5A protein interacts with -catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion

Milward

Mankouri

Harris

2009

Journal of General Virology

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Hepatitis C virus (HCV) infection is increasingly associated with the development of hepatocellular carcinoma (HCC). HCV is not thought to be directly oncogenic but, by modulating a range of cellular functions, may predispose patients to the development of liver tumours. However, the molecular mechanisms by which HCV infection might contribute to HCC remain to be characterized. In this regard, we showed previously that the HCV NS5A protein bound to the p85 regulatory subunit of phosphoinositide-3 kinase (PI3K), thereby stimulating the activity of the p110 catalytic subunit of the enzyme. One of the downstream consequences of this was the stabilization of the proto-oncogene, b-catenin, with a concomitant stimulation of its transcriptional activity. Here, we further analyse the mechanism by which NS5A mediates activation of b-catenin. Although our previous data were consistent with a role for the PI3K downstream effector kinases, Akt and glycogen synthase kinase-3b, in NS5A-mediated activation of b-catenin, we demonstrate here that it is in fact independent of both of these kinases. Truncation analysis revealed that both the N and C termini of NS5A are required for full activation of b-catenin. Furthermore, we demonstrate that NS5A, either alone or in complex with p85, is able to bind directly to b-catenin; again both N and C termini contribute to this interaction. We propose that NS5A activates bcatenin via a novel mechanism that involves a direct interaction between the two proteins and is augmented by PI3K activity. This may contribute to the association between chronic HCV infection and the development of HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus NS5A protein interacts with -catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion

Milward

Mankouri

Harris

2009

Journal of General Virology

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“…TBL1 Inhibits Siah-1-mediated ␤-Catenin Degradation in Cells-It has previously been shown that expression of Siah-1 correlates with reduced levels of ␤-catenin in cells (7)(8)(9)28). Overexpression of Siah-1 in the absence of a Wnt ligand reduced levels of ␤-catenin and lowered the induction of Tcf/ Lef target genes (7,8).…”

Section: ␤-Catenin Ubiquitination By Siah-1 Protection By Tbl1mentioning

confidence: 99%

“…p53 directly induces the expression of Siah-1 and in turn formation of a unique SCF-like complex (SCF(TBL1)) comprised of Siah-1, Siah-1-interacting protein (SIP), Skp1, transducin ␤-like 1 (TBL1), and APC (7,8). The physiological significance of Siah-1-targeted degradation of ␤-catenin is underscored by the discovery that this pathway is directly targeted by the viral oncoprotein latent membrane protein 1 (LMP1) (9). In addition, recent studies identified two drugs, hexachlorophene and isoreserpine, which attenuate the function of ␤-catenin through activation of Siah-1 and subsequent proteasomal degradation (10,11).…”

mentioning

confidence: 99%

Direct Ubiquitination of β-Catenin by Siah-1 and Regulation by the Exchange Factor TBL1

Dimitrova

Lee

et al. 2010

Journal of Biological Chemistry

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␤-Catenin is a key component of the Wnt signaling pathway that functions as a transcriptional co-activator of Wnt target genes. Upon UV-induced DNA damage, ␤-catenin is recruited for polyubiquitination and subsequent proteasomal degradation by a unique, p53-induced SCF-like complex (SCF(TBL1)), comprised of Siah-1, Siah-1-interacting protein (SIP), Skp1, transducin ␤-like 1 (TBL1), and adenomatous polyposis coli (APC). Given the complexity of the various factors involved and the novelty of ubiquitination of the non-phosphorylated ␤-catenin substrate, we have investigated Siah-1-mediated ubiquitination of ␤-catenin in vitro and in cells. Overexpression and purification protocols were developed for each of the SCF(TBL1) proteins, enabling a systematic analysis of ␤-catenin ubiquitination using an in vitro ubiquitination assay. This study revealed that Siah-1 alone was able to polyubiquitinate ␤-catenin. In addition, TBL1 was shown to play a role in protecting ␤-catenin from Siah-1 ubiquitination in vitro and from Siah-1-targeted proteasomal degradation in cells. Siah-1 and TBL1 were found to bind to the same armadillo repeat domain of ␤-catenin, suggesting that polyubiquitination of ␤-catenin is regulated by competition between Siah-1 and TBL1 during Wnt signaling.

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“…Recently, ␤-catenin, which is a ligand-dependent coactivator of AR, has been shown to interact with HIF-1␣ (20,21). ␤-Catenin is much more highly expressed in prostate cancer, compared with normal prostate tissue (4,23). In the present study, we investigated whether HIF-1␣ and ␤-catenin coordinately enhance the transcriptional activity of AR at a low DHT level in prostate cancer cells.…”

mentioning

confidence: 99%

Coordinated Action of Hypoxia-inducible Factor-1α and β-Catenin in Androgen Receptor Signaling

Mitani

Harada

Nakano

et al. 2012

Journal of Biological Chemistry

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Background:The mechanism that regulates androgen receptor (AR) function in castration-resistant prostate cancer (CRPC) remains unclear. Results: Hypoxia-inducible factor (HIF)-1␣ enhances ␤-catenin-mediated AR transactivation and promotes nuclear translocation of ␤-catenin. Conclusion: Coordinated action of HIF-1␣ and ␤-catenin contributes to AR function in CRPC. Significance: The novel functions of HIF-1␣ in AR signaling are important for understanding the development of CRPC.

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Up-regulation of β-catenin by a viral oncogene correlates with inhibition of the seven in absentia homolog 1 in B lymphoma cells

Cited by 50 publications

References 36 publications

Hepatitis C virus NS5A protein interacts with -catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion

Hepatitis C virus NS5A protein interacts with -catenin and stimulates its transcriptional activity in a phosphoinositide-3 kinase-dependent fashion

Direct Ubiquitination of β-Catenin by Siah-1 and Regulation by the Exchange Factor TBL1

Coordinated Action of Hypoxia-inducible Factor-1α and β-Catenin in Androgen Receptor Signaling

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