Structure and expression of the human gene for the matrix metalloproteinase matrilysin.
Matrilysin, a member of the matrix metalloproteinase family, is structurally different from the other matrix metalloproteinases by virtue of the absence of a conserved COOH-terminal protein domain. In addition, matrilysin mRNA is regulated in a specific and distinct manner in normal and malignant tissues. Analysis of the genomic structure of the human matrilysin gene revealed that the organization of the first five exons is highly conserved among the different members of the matrix metalloproteinase family, but that matrilysin contains an atypical sixth exon. The promoter region of the matrilysin gene has several features that are conserved among several other matrix metalloproteinase family members, including the presence of TATA, AP-1, and PEA3 elements. Comparison of the expression of the human matrilysin promoter with rat stromelysin promoter/chloramphenicol acetyltransferase constructs in HeLa cells revealed that constructs containing AP-1 and PEA3 elements respond similarly to epidermal growth factor and tumor promoter (12-O-tetradecanoyl-phorbol-13-acetate) induction, but that the addition of upstream stromelysin sequences results in an increased transcriptional activity not observed with upstream matrilysin sequences. The similarities and differences observed between the promoters of matrilysin and the other metalloproteinases may provide insights into the molecular mechanisms that regulate the expression of this family of enzymes as a whole and the factors that distinguish the expression patterns of individual family members.
Gaire
M
M
Department of Cell Biology, Vanderbilt University, Nashville, Tennessee 37232.
Magbanua
Z
Z
McDonnell
S
S
McNeil
L
L
Lovett
D H
DH
Matrisian
L M
LM
D000818:Animals; D001483:Base Sequence; D001943:Breast Neoplasms; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers; D005091:Exons; D005260:Female; D015870:Gene Expression; D015971:Gene Expression Regulation, Enzymologic; D005809:Genes, Regulator; D015698:Genomic Library; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D007438:Introns; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics*; D008969:Molecular Sequence Data; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D012689:Sequence Homology, Nucleic Acid; D016385:TATA Box; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012333:RNA, Messenger; D004247:DNA; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7