National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan 704, Taiwan.
Biochem Biophys Res Commun. 2013 Jul 12;436(4):672-6. doi: 10.1016/j.bbrc.2013.06.014. Epub 2013 Jun 11.
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.
WW 结构域包含氧化还原酶（WOX1）参与肿瘤抑制和许多其他生物学功能，但它与病毒蛋白的分子和功能相互作用在很大程度上仍是未知的。本研究揭示了 WOX1 与潜伏膜蛋白 2A（LMP2A），即 EBV 的一种癌蛋白，在物理上相互作用。这种分子相互作用涉及 WOX1 的酪氨酸残基 33 和 LMP2A 的富含脯氨酸的基序。有趣的是，内源性 WOX1 是 LMP2A 触发的一些促进癌症的效应所必需的，包括细胞外信号调节激酶 1/2 的激活、基质金属蛋白酶 9（MMP9）的上调和促进细胞侵袭。内源性 WOX1 敲低后，LMP2A 触发的 MMP9 诱导可被外源性野生型 WOX1 恢复，但不能被与 LMP2A 结合缺陷的 WOX1 突变体恢复。这些结果表明，通过与 LMP2A 的相互作用，WOX1 参与 MMP9 的诱导，提示 WOX1 在 EBV 相关癌症进展中的一个新作用。
