Structure and Characterization of the Human Tissue Inhibitor of Metalloproteinases-2 Gene

作者: Khalil Hammani , Andrew Blakis , Delmore Morsette , Anne M. Bowcock , Christoph Schmutte

DOI: 10.1074/JBC.271.41.25498

关键词:

摘要: We report here the characterization of human tissue inhibitor metalloproteinases-2 (TIMP-2) gene. The gene is 83 kilobase pairs (kb) long with exon-intron splicing sites located in preserved positions among three members TIMP family. A 2.6-kb genomic DNA fragment flanking 5'-end contains several regulatory elements including five Sp1, two AP-2, one AP-1, and PEA-3 binding sites. Despite presence a complete AP-1 consensus at position -281, promoter did not respond to 12-O-tetradecanoylphorbol-13-acetate treatment. However, response was generated by insertion similar -71, indicating importance positioning this motif. typical CpG island; however, methylation island seem influence expression. Analysis 3'-end revealed that mRNAs for TIMP-2 (1.2 3.8 kb) differ selection their polyadenylation signal sites, but these does affect RNA stability. In summary, has features observed housekeeping genes, differs significantly from TIMP-1 TIMP-3 genes. These differences are likely explain specific roles inhibitors play regulation matrix metalloproteinases.

参考文章(48)
Thomas E. Ahlering, Louis Dubeau, Peter A. Jones, A New in Vivo Model to Study Invasion and Metastasis of Human Bladder Carcinoma Cancer Research. ,vol. 47, pp. 6660- 6665 ,(1987)
Yi Sun, Glenn Hegamyer, Hyungtae Kim, Kavitha Sithanandam, Hua Li, Rebecca Watts, Nancy H. Colburn, Molecular Cloning of Mouse Tissue Inhibitor of Metalloproteinases-3 and Its Promoter SPECIFIC LACK OF EXPRESSION IN NEOPLASTIC JB6 CELLS MAY REFLECT ALTERED GENE METHYLATION Journal of Biological Chemistry. ,vol. 270, pp. 19312- 19319 ,(1995) , 10.1074/JBC.270.33.19312
M Wick, R Härönen, D Mumberg, C Bürger, B R Olsen, M L Budarf, S S Apte, R Müller, Structure of the human TIMP-3 gene and its cell cycle-regulated promoter. Biochemical Journal. ,vol. 311, pp. 549- 554 ,(1995) , 10.1042/BJ3110549
C E Campbell, A M Flenniken, D Skup, B R Williams, Identification of a serum- and phorbol ester-responsive element in the murine tissue inhibitor of metalloproteinase gene. Journal of Biological Chemistry. ,vol. 266, pp. 7199- 7206 ,(1991) , 10.1016/S0021-9258(20)89630-6
W.G. Stetler-Stevenson, P.D. Brown, M. Onisto, A.T. Levy, L.A. Liotta, Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. Journal of Biological Chemistry. ,vol. 265, pp. 13933- 13938 ,(1990) , 10.1016/S0021-9258(18)77438-3
K.J. Leco, R. Khokha, N. Pavloff, S.P. Hawkes, D.R. Edwards, Tissue inhibitor of metalloproteinases-3 (TIMP-3) is an extracellular matrix-associated protein with a distinctive pattern of expression in mouse cells and tissues. Journal of Biological Chemistry. ,vol. 269, pp. 9352- 9360 ,(1994) , 10.1016/S0021-9258(17)37115-6
H. Birkedal-Hansen, W.G.I. Moore, M.K. Bodden, L.J. Windsor, B. Birkedal-Hansen, A. DeCarlo, J.A. Engler, Matrix Metalloproteinases: A Review Critical Reviews in Oral Biology & Medicine. ,vol. 4, pp. 197- 250 ,(1993) , 10.1177/10454411930040020401