Human stromelysin-1 promoter

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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4351723, 4353201, 435325, 435366, 4352523, 536 235, C07H 2104, C12N 516, C12N 1512, C12N 1585

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058247947

ABSTRACT:
This invention relates to a human stromelysin-1 (i.e., HSL-1) promoter and uses therefor. In particular, the invention provides a purified DNA containing a functional HSL-1 promoter region that corresponds in structure to the native genomic form of this promoter, an expression vector containing a portion of the purified promoter DNA operatively linked to a heterologous DNA sequence encoding a detectable gene product, a host cell transformed with this factor , a pharmacologic screening assay for stromelysin-1 promoter modulating activity, and a method of modulating TNF .alpha. level and matrix metalloproteinase activities in inflamed tissues of a mammal.

REFERENCES:
Borden P, et al. "The human stromelysin promoter contains a previously unreported 1.0 kb sequence." Gene 151: 315-320, 1994.
Quinones S, et al. "Transcriptional regulation of human stromelysin." JBC 264 (14): 8339-8344, 1989.
Birkedal-Hansen H, et al. "Matrix metalloproteinases: A review." Crit. Rev. Oral Biol. and Med 4(2): 197-250, 1993.
Quinones, et al., "Transcriptional Regulation of Human Stromelysin", (1989) J. Bio. Chem. 264: 8339-8344.
Buttice, et al., "The AP-1 site is required for basal expression but is not necessary for TPA-response of the human stromelysin gene", (1991) Nucleic Acids Res. 19:3723-3731.
Frisch and Ruley, "Transcription from the Stromelysin Promoter Is Induced by Interleukin-1 and Repressed by Dexamethasone", (1987) J. Bio. Chem. 262:16300-16304.
Buttice and Kurkinen, "A Polyomavirus Enhancer A-binding Protein-3 Site and Ets-2 Protein Have a Major Role in the 12-0-Tetradecanoylphorbol-13-acetate Reponse of the Human Stromelysin Gene", (1993) J. Biol. Chem. 268: 7196-7204.
Birkedal-Hansen, et al., "Matrix Metalloproteinases: A Review", (1993) Crit. Revs. in Oral Biol. & Med. 4(2):197-250.
Sirum-Connolly and Brinckerhoff, "Interleukin-1 or phorbol induction of the stromelysin promoter requires an element that cooperates with AP-1", (1991) Nucleic Acids Res. 19:335-341.
Sirum and Brinckerhoff, "Cloning of the Genes for Human Stromelysin and Stromelysin 2: Differential Expression in Rheumatoid Synovial Fibroblasts", (1989) Biochem. 28:8691-8698.
Diaz-Meco, et al., "Protein Kinase C-independent Expression of Stromelysin by Platelet-derived Growth Factor, ras Oncogene, and Phosphatidylcholine-hydrolyzing Phospholipase C" (1991) J. Biol. Chem. 266:22597-22602.
Matrisian, et al., "Isolation of the Oncogene and Epidermal Growth Factor-Induced Transin Gene: Complex Control in Rat Fibroblasts", (1986) Mol. & Cell. Bio. 6:1679-1686.

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