Tissue transglutaminase-induced down-regulation of matrix metalloproteinase-9.
Tissue transglutaminase (TGase 2) has been reported to have multiple functions in addition to its function as a biological adhesive. To identify its roles, we investigated the effects of TGase 2 on gelatinase activity. The MMP-9 activity of certain cell lines was significantly inhibited with retinoic acid treatment, and this effect was reversed in the presence of a TGase 2 inhibitor. Furthermore, TGase 2 overexpression reduced the MMP-9 protein expression levels and inhibited its activity in both culture media and cell lysate. The decreased mRNA levels of MMP-9 and the results of a promoter assay revealed that TGase 2 may be involved in MMP-9 transcription. Further, data obtained in an immunoprecipitation assay and an electrophoretic mobility shift assay demonstrated that TGase 2 binds to c-Jun and suppresses its binding activity toward AP-1. These results suggest that TGase 2 inhibits MMP-9 via downregulation of MMP-9 transcription activity by blocking the binding of the Jun-fos complex to an AP-1 site.
Ahn
Jun-Seok
JS
Department of Anatomy and Cell Biology, Kangwon National University, College of Medicine, Hyoja 2 Dong, Chunchon 200-701, Republic of Korea.
Kim
Min-kyung
MK
Hahn
Jang-hee
JH
Park
Jung-Hyeun
JH
Park
Kyeong-Han
KH
Cho
Byung-Ryul
BR
Park
Seung-Bae
SB
Kim
Dae-joong
DJ
D001665:Binding Sites; D002460:Cell Line; D003470:Culture Media; D015536:Down-Regulation; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D061965:Matrix Metalloproteinase Inhibitors; D011401:Promoter Regions, Genetic; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014158:Transcription, Genetic; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*
D003470:Culture Media; D061965:Matrix Metalloproteinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D020780:Matrix Metalloproteinase 9; D019204:GTP-Binding Proteins