Involvement of Sp1 elements in the promoter activity of the α1-proteinase inhibitor gene

被引:30
|
作者
Li, YH
Zhou, LL
Twining, SS
Sugar, J
Yue, BYJT [1 ]
机构
[1] Univ Illinois, Coll Med, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA
[2] Med Coll Wisconsin, Dept Biochem, Milwaukee, WI 53226 USA
[3] Med Coll Wisconsin, Dept Ophthalmol, Milwaukee, WI 53226 USA
关键词
D O I
10.1074/jbc.273.16.9959
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The transcripts of the alpha(1)-proteinase inhibitor in the cornea are different from those in hepatocytes and monocytes, suggesting that alpha(1)-proteinase inhibitor gene transcription may respond to different cell-specific regulatory mechanisms. Although information on alpha(1)-proteinase inhibitor gene structure has been obtained, little is known regarding the cis- and trans-acting factors that regulate its expression. In this study, we cloned and sequenced a 2,7-kilobase 5'-flanking region upstream from the corneal transcription initiation site of the gene, demonstrated functional promoter activity, and identified the regulatory elements. Sequencing revealed that the 5'-flanking element was highly G/C-rich in regions proximal to the corneal transcription start site. DNase I footprinting located 10 potential Spl-binding sites between nucleotides -1519 and +44. The putative promoter was functional in human corneal stromal cells, but not in human skin, scleral, and conjunctival fibroblasts, suggesting that the promoter may be corned cell-specific. The promoter activity in the corneal cells was repressed when Spl was coexpressed. In the cornea-thinning disease keratoconus, down-regulation of the alpha(1)-proteinase inhibitor gene and increased Spl expression have both been demonstrated. The current results suggest that down-regulation of the inhibitor in keratoconus corneas may be related directly to overexpression of the Spl gene. This information may help elucidate the molecular pathways leading to the altered alpha(1)-proteinase inhibitor expression in keratoconus.
引用
收藏
页码:9959 / 9965
页数:7
相关论文
共 50 条
  • [41] Conformational changes of ovine α-1-proteinase inhibitor: The influence of heparin binding
    Gupta, Vivek Kumar
    Gowda, Lalitha R.
    JOURNAL OF MOLECULAR STRUCTURE, 2008, 891 (1-3) : 456 - 462
  • [42] α1-proteinase inhibitor mutants with specificity for plasma kallikrein and Cls but not Cl
    Sulikowski, T
    Bauer, BA
    Patston, PA
    PROTEIN SCIENCE, 2002, 11 (09) : 2230 - 2236
  • [43] Characterization of differences in isoelectric focusing behavior of α1-proteinase inhibitor products
    Marszal, E
    Shrake, A
    TRANSFUSION, 2006, 46 (05) : 872 - 873
  • [44] Fecal α1-proteinase inhibitor concentration in dogs with chronic gastrointestinal disease
    Murphy, KF
    German, AJ
    Ruaux, CG
    Steiner, JM
    Williams, DA
    Hall, EJ
    VETERINARY CLINICAL PATHOLOGY, 2003, 32 (02) : 67 - 72
  • [45] Influence of the P5 residue on α1-proteinase inhibitor mechanism
    Chaillan-Huntington, CE
    Patston, PA
    JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (08) : 4569 - 4573
  • [46] CREB and Sp1 regulate the human MAP gene promoter activity in renal tubular epithelial cells
    Lu, Chao
    Ren, Wei
    Su, Xing-Ming
    Chen, Jie-Qing
    Wu, Sheng-Hua
    Guo, Xi-Rong
    Huang, Song-Ming
    Chen, Long-Hua
    Zhou, Guo-Ping
    ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2008, 474 (01) : 143 - 149
  • [47] Glucosamine activates the plasminogen activator inhibitor 1 gene promoter through Sp1 DNA binding sites in glomerular mesangial cells
    Goldberg, HJ
    Scholey, J
    Fantus, IG
    DIABETES, 2000, 49 (05) : 863 - 871
  • [48] Characterization of the neuropilin-1 promoter;: gene expression is mediated by the transcription factor Sp1
    Rossignol, M
    Pouysségur, J
    Klagsbrun, M
    JOURNAL OF CELLULAR BIOCHEMISTRY, 2003, 88 (04) : 744 - 757
  • [49] Characterization of differences in isoelectric focusing behavior of α1-proteinase inhibitor products -: Reply
    Walsh, JW
    Sandhaus, RA
    Trapnell, B
    TRANSFUSION, 2006, 46 (05) : 874 - 874
  • [50] Conformational change in elastase following complexation with α1-proteinase inhibitor:: a CD investigation
    Bousquet, JA
    Duranton, J
    Mély, Y
    Bieth, JG
    BIOCHEMICAL JOURNAL, 2003, 370 (370) : 345 - 349