WW domain-containing oxidoreductase is involved in upregulation of matrix metalloproteinase 9 by Epstein–Barr virus latent membrane protein 2A

Lan, Yung Chiang; Wu, Shih Yi; Lai, Heng; Chang, Nan Shan; Chang, Fang; Tsai, Meng Hsuan; Su, Ih Jen; Chang, Yao

doi:10.1016/j.bbrc.2013.06.014

Cited by 13 publications

(18 citation statements)

References 27 publications

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“…Moreover, in the current study, our result shown that SNP rs12918952 in WWOX conferred higher risk of vascular invasion, however, no difference was found regarding the HBsAg and anti-hepatitis C virus (Table 4). WWOX is known to regulate virus-associated immunodeficiency and various cancers, including HCC [9, 48–51]. Further investigation is warranted to explore the potential role of WWOX polymorphism and viral regulation of HCC progression.…”

Section: Discussionmentioning

confidence: 99%

Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk

et al. 2017

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BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene in multiple cancers. We hypothesize that genetic variations in WWOX are associated with HCC risk.Methodology/Principal findingsFive single-nucleotide polymorphisms (SNPs) of the WWOX gene were evaluated from 708 normal controls and 354 patients with HCC. We identified a significant association between a WWOX single nucleotide polymorphism (SNP), rs73569323, and decreased risk of HCC. After adjustment for potential confounders, patients with at least one T allele at rs11545028 of WWOX may have a significantly smaller tumor size, reduced levels of α-fetoprotein and alanine aminotransferase (ALT). Moreover, the A allele at SNP rs12918952 in WWOX conferred higher risk of vascular invasion. Additional in silico analysis also suggests that WWOX rs12918952 polymorphism tends to affect WWOX expression, which in turn contributes to tumor vascular invasion.ConclusionsIn conclusion, genetic variations in WWOX may be a significant predictor of early HCC occurrence and a reliable biomarker for disease progression.

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Section: Discussionmentioning

confidence: 99%

Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk

et al. 2017

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“…They report that WOX1 is important for cancer-promoting effects triggered by LMP2A and, specifically, that the PPxY/WW-domain interactions between LMP2A and WOX1 were important for induction of matrix metalloproteinase 9 (MMP9). These findings suggest that the modular interactions between the PPxY motifs of EBV LMP2A and the WW domain on host WOX1 may be crucial for invasiveness and cancer progression associated with EBV infection (130).…”

Section: Epstein-barr Virus (Ebv; Human Gammaherpesvirus 4)-mentioning

confidence: 86%

“…More recently, Lan et al (130) described an intriguing interaction between the PPxY motifs of EBV LMP2A and a host WW domain-containing oxidoreductase (WOX1) that functions, in part, as a tumor suppressor. They report that WOX1 is important for cancer-promoting effects triggered by LMP2A and, specifically, that the PPxY/WW-domain interactions between LMP2A and WOX1 were important for induction of matrix metalloproteinase 9 (MMP9).…”

Section: Epstein-barr Virus (Ebv; Human Gammaherpesvirus 4)-mentioning

confidence: 99%

Viruses go modular

Shepley-McTaggart

Fan

Sudol

et al. 2020

Journal of Biological Chemistry

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The WW domain is a modular protein structure that recognizes the proline-rich Pro-Pro-x-Tyr (PPxY) motif contained in specific target proteins. The compact modular nature of the WW domain makes it ideal for mediating interactions between proteins in complex networks and signaling pathways of the cell (e.g. the Hippo pathway). As a result, WW domains play key roles in a plethora of both normal and disease processes. Intriguingly, RNA and DNA viruses have evolved strategies to hijack cellular WW domain-containing proteins and thereby exploit the modular functions of these host proteins for various steps of the virus life cycle, including entry, replication, and egress. In this review, we summarize key findings in this rapidly expanding field, in which new virus-host interactions continue to be identified. Further unraveling of the molecular aspects of these crucial virus-host interactions will continue to enhance our fundamental understanding of the biology and pathogenesis of these viruses. We anticipate that additional insights into these interactions will help support strategies to develop a new class of small-molecule inhibitors of viral PPxY-host WW-domain interactions that could be used as antiviral therapeutics. . 2 The abbreviations used are: PPxY, proline-proline-x-tyrosine motif; AdV, adenovirus; ART protein, arrestin-related trafficking protein; BAG3, BCL2associated athanogene 3; BUL1 and -2, binds ubiquitin ligase proteins 1 and 2; CASA, chaperone-assisted selective autophagy; CIRF, cell-intrinsic restriction factor; EBV, Epstein-Barr virus; EBOV, Ebola virus; ESCRT, endosomal sorting complex required for transport; HECT, homologous to the E6AP carboxyl terminus (E3 ligase family); HHV, human herpes virus; HTLV-1, human T-cell leukemia virus 1; IFITM3, interferon-induced transmembrane protein 3; ISG15, interferon stimulated gene 15; ITCH (AIP4), Itchy E3 ubiquitin protein ligase; LDI-1 and -2, late domain-interacting proteins 1 and 2; L domain, viral late domain; LMP2A, latent membrane protein 2A; MARV, Marburg virus; MLV, murine leukemia virus; Nedd4, neuronal precursor cell-expressed developmentally down-regulated 4; PVI, preprotein VI (membrane lytic internal capsid protein); Rsp5, yeast reverses SPTphenotype protein 5 (E3 ubiquitin-protein ligase); RSV, Rous sarcoma virus; SMURF1 and -2, Smad ubiquitin-regulating factors 1 and 2; TBSV, tomato bushy stunt virus; Tsg101, tumor susceptibility gene 101; VLP, virus-like particle; VSV, vesicular stomatitis virus; WOX1, WW domain-containing oxidoreductase; WWP1 and -2, WW domain-containing E3 ubiquitin protein ligase 1 and 2; MS, multiple sclerosis. cro REVIEWS 4604

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“…Por tanto, al actuar como un BCR activado, LMP2A aumenta la activación temprana, proliferación y supervivencia de células B, favoreciendo el establecimiento de LCLs. LMPA2 también es capaz de interactuar con el residuo 33 de WOX-1 un supresor tumoral, a través de sus regiones PY, desatando la activación de ERK1/2 y cascada abajo el factor de transcripción Fra-1, lo que conduce a un aumento en la expresión de metaloproteinasa (MMP) 9, proteína implicada en la invasión celular 47 .…”

Section: Proteína Latente De Membrana 2 (Lmp2): Lmp2unclassified

Revisión sistemática: estrategias virales para la inducción de cáncer “virus de Epstein-Barr: latencia y mecanismos asociados a la oncogénesis viral”

Rincón-Orozco

2018

revsal

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La infección crónica con virus oncogénicos es responsable de aproximadamente el 20% de todos los cánceres reportados en humanos, este proceso de oncogénesis viral presenta una naturaleza compleja, multietapa y multifactorial. Un ejemplo de ello es el Virus de Epstein-Barr (EBV), un herpesvirus que infecta de manera latente a más del 90% de la población. Aunque la infección a menudo cursa de manera asintomática, el EBV es capaz de modificar su expresión genómica estableciendo diferentes fases de latencia, alterando así el metabolismo de sus células blanco, como son los linfocitos B y las células epiteliales, proceso que resulta determinante en la aparición y desarrollo de diferentes patologías que van desde la mononucleosis infecciosa hasta procesos oncológicos como el linfoma de Burkitt, el cáncer gástrico o el cáncer nasofaríngeo.

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WW domain-containing oxidoreductase is involved in upregulation of matrix metalloproteinase 9 by Epstein–Barr virus latent membrane protein 2A

Cited by 13 publications

References 27 publications

Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk

Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk

Viruses go modular

Revisión sistemática: estrategias virales para la inducción de cáncer “virus de Epstein-Barr: latencia y mecanismos asociados a la oncogénesis viral”

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