title: WW domain-containing oxidoreductase is involved in upregulation of matrix metalloproteinase 9 by Epstein-Barr virus latent membrane protein 2A.
abstract: WW domain-containing oxidoreductase (WOX1) participates in tumor suppression and many other biologic functions, but its molecular and functional interactions with viral proteins remain largely unknown. This study reveals that WOX1 is physically associated with latent membrane protein 2A (LMP2A), an oncoprotein of Epstein-Barr virus. The molecular interaction involves the tyrosine residue 33 of WOX1 and the proline-rich motifs of LMP2A. Interestingly, endogenous WOX1 is required for some LMP2A-triggered, cancer-promoting effects, including activation of extracellular signal-regulated kinase-1/2, upregulation of matrix metalloproteinase 9 (MMP9) and promotion of cell invasion. Upon knockdown of endogenous WOX1, LMP2A-triggered MMP9 induction is restored by exogenous wild-type WOX1, but not by a WOX1 mutant defective in LMP2A binding. These results indicate that, through interaction with LMP2A, WOX1 is involved in MMP9 induction, suggesting a novel role of WOX1 in Epstein-Barr virus-associated cancer progression.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 704, Taiwan.
authors.forename: Yu-Yan
authors.initials: YY
authors.lastname: Lan
authors.forename: Shih-Yi
authors.initials: SY
authors.lastname: Wu
authors.forename: Hsiao-Ching
authors.initials: HC
authors.lastname: Lai
authors.forename: Nan-Shan
authors.initials: NS
authors.lastname: Chang
authors.forename: Fang-Hsin
authors.initials: FH
authors.lastname: Chang
authors.forename: Meng-Hsuan
authors.initials: MH
authors.lastname: Tsai
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
authors.forename: Yao
authors.initials: Y
authors.lastname: Chang
mesh_terms: D001483:Base Sequence; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D010088:Oxidoreductases / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000502:physiology*; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000378:metabolism*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D034741:RNA, Small Interfering; D025521:Tumor Suppressor Proteins; D014763:Viral Matrix Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human; D020780:Matrix Metalloproteinase 9
keywords: EBV; ECM; ERK; Epstein–Barr virus; LMP2A; Latent membrane protein 2A; MMP; Matrix metalloproteinase 9; NPC; WOX1; WW domain-containing oxidoreductase; extracellular matrix; extracellular signal-regulated kinase; latent membrane protein 2A; matrix metalloproteinase; nasopharyngeal carcinoma; siRNA; small interfering RNA