Structural Analysis and Promoter Characterization of the Human Collagenase3 Gene (MMP13 (original) (raw)

The matrix metalloproteinases (MMPs) 2 constitute a composed of 10 exons and 9 introns and spans over family of structurally related zinc-dependent endopep-12.5 kb. The overall organization of the collagenasetidases that play a major role in the remodeling of the 3 gene is similar to that of other MMP genes clustered connective tissue occurring in many normal processes at chromosome 11q22, including fibroblast collagenlike embryonic growth and development, wound healase (MMP-1), matrilysin (MMP-7), and macrophage ing, bone growth and resorption, and uterine involution metalloelastase (MMP-12), but is more distantly re- (Woessner, 1991;; Birkedal-Hansen et lated to genes coding for stromelysin-3 (MMP-11), al., 1993). In addition, abnormal expression of these gelatinase-A (MMP-2), and gelatinase-B (MMP-9), proteolytic enzymes may contribute to a variety of which map outside of this gene cluster. Nucleotide pathological processes such as rheumatoid arthritis sequence analysis of about 1 kb of the 5-flanking re-(Murphy and Hembry, 1992), atherosclerosis (Henney gion of the collagenase-3 gene revealed the presence et al., 1991), and tumor invasion and metastasis (Liotta of a TATA box, an AP-1 motif, a PEA-3 consensus se- et al., 1991). Recently, we have reported the cloning of quence, an osteoblast specific element (OSE-2), and a human gene coding for a novel member of this family a TGF-b inhibitory element. Transient transfection of proteolytic enzymes that has been designated collaexperiments in HeLa and COS-1 cells with chloramgenase-3 (MMP13) , since it reprephenicol acetyltransferase (CAT)-containing consents the third member of the collagenase subfamily structs showed that the AP-1 site is functional and of MMPs, the others being fibroblast and neutrophil responsible for the observed inducibility of the recollagenases (Goldberg et al., 1986;.