Molecular characterization of a novel transcription factor that controls stromelysin expression.

TitleMolecular characterization of a novel transcription factor that controls stromelysin expression.
Publication TypeJournal Article
Year of Publication1995
AuthorsSanz L, Moscat J, Diaz-Meco MT
JournalMol Cell Biol
Date Published1995 Jun
Keywords3T3 Cells, Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, DNA, Complementary, Gene Expression Regulation, Enzymologic, Matrix Metalloproteinase 3, Metalloendopeptidases, Mice, Molecular Sequence Data, Transcription Factors

Stromelysins, which are the metalloproteinases with the widest substrate specificities, play a critical role in tumor invasion and metastasis. We have previously reported an element (SPRE) of the stromelysin promoter located between nucleotides -1221 and -1203 that is necessary and sufficient for the control of stromelysin gene expression by mitogenic activation, which induces a nuclear activity that binds to this sequence. Using a concatenated probe with several copies of this element to screen a lambda gt11 cDNA expression library from mouse Swiss 3T3 fibroblasts, we report here the molecular cloning of a cDNA coding for a novel protein (SPBP) of 937 amino acids that binds to this element and has several features of a transcription factor, such as a putative leucine zipper region, a nuclear localization signal, and a basic domain with homology to the DNA-binding domains of Fos and Jun. Evidence that SPBP is at least a critical component of the mitogen-induced SPRE nuclear binding activity is presented here. Furthermore, the transfection of an expression plasmid for SPBP transactivates reporter chloramphenicol acetyltransferase plasmids containing either the full-length stromelysin promoter or a single copy of the SPRE cloned upstream of the herpes simplex virus thymidine kinase minimal promoter. Therefore, the results presented here identify a novel transcription factor critically involved in the control of stromelysin expression.

Alternate JournalMol Cell Biol
PubMed ID7760812
PubMed Central IDPMC230548
Related Faculty: 
Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

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