Molecular Biology Reports

, Volume 27, Issue 3, pp 167–173

Characterization of 5′-flanking region of human aggrecanase-1 (ADAMTS4) gene

  • Yoshiharu Mizui
  • Kazuto Yamazaki
  • Yoshikazu Kuboi
  • Koji Sagane
  • Isao Tanaka
Article

DOI: 10.1023/A:1007253930568

Cite this article as:
Mizui, Y., Yamazaki, K., Kuboi, Y. et al. Mol Biol Rep (2000) 27: 167. doi:10.1023/A:1007253930568

Abstract

Aggrecanase-1, also known as ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs 4), cleaves at the Glu373-Ala374 site of aggrecan, thereby indicating aggrecan degradation. It is thought that ADAMTS4 plays a pivotal role in inflammatory joint diseases and cartilage degradation. To elucidate the mechanisms of regulation of ADAMTS4 gene expression, we cloned the 5′-flanking region of the human ADAMTS4 gene and characterized its promoter activity by means of reporter assay using porcine chondrocytes and NIH3T3 cells. Reporter gene analysis using deletion variants suggested that the region between −383 and +10 relative to the tentative transcription start site is necessary for full promoter activity; this region contains one Sp1 and three AP2 sites. In addition, the segment between −726 and −384 appears to contain silencer element(s). A complete deletion mutant of the nuclear factor I (NFI) binding site at −441 to −429 resulted in recovery of the promoter activity in chondrocytes, but not in NIH3T3 cells. Thus, the NFI site is involved in negative regulation of the human ADAMTS4 promoter activity in chondrocytes.

aggrecanase-1ADAMTS4promotersilencernuclear factor I

Copyright information

© Kluwer Academic Publishers 2000

Authors and Affiliations

  • Yoshiharu Mizui
    • 1
  • Kazuto Yamazaki
    • 1
  • Yoshikazu Kuboi
    • 1
  • Koji Sagane
    • 1
  • Isao Tanaka
    • 1
  1. 1.Tsukuba Research LaboratoriesEisai Co., Ltd.IbarakiJapan