TY - JOUR
T1 - WW domain-containing oxidoreductase is involved in upregulation of matrix metalloproteinase 9 by Epstein-Barr virus latent membrane protein 2A
AU - Lan, Yu Yan
AU - Wu, Shih Yi
AU - Lai, Hsiao Ching
AU - Chang, Nan Shan
AU - Chang, Fang Hsin
AU - Tsai, Meng Hsuan
AU - Su, Ih Jen
AU - Chang, Yao
N1 - Funding Information:
This study was supported by the National Science Council, Taiwan ( NSC99-2628-B-400-001-MY3 ) and the National Health Research Institutes, Taiwan ( IV-101-PP-18 and IV-102-PP-19 ).
PY - 2013/7/12
Y1 - 2013/7/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84880047211
UR - https://www.scopus.com/pages/publications/84880047211#tab=citedBy
U2 - 10.1016/j.bbrc.2013.06.014
DO - 10.1016/j.bbrc.2013.06.014
M3 - Article
C2 - 23770367
AN - SCOPUS:84880047211
SN - 0006-291X
VL - 436
SP - 672
EP - 676
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -
