The human and mouse matrix metalloproteinase MMP-21: the structure and the regulation of the gene and the protein

Summary Metalloproteinases (MMPs) play key roles in tissue remodeling under normal development and, especially, in diseases ranging from malignancies to stroke. We cloned and thoroughly characterized the novel human and mouse MMP gene encoding matrix metalloproteinase-21 (MMP-21). MMP-21 is the last uncharacterized MMP coded by human genome. Human and mouse MMP-21 is the orthologue of Xenopus laevis X-MMP. The latent proenzyme of MMP-21 (569 amino acid residues) consists of the prodomain, the catalytic domain and the hemopexinlike domain, and is potentially capable of being activated in its secretory pathway to the extracellular millieu by furin-like proprotein convertases. Human MMP-21 is the likely target gene of the Wnt pathway. In addition, the expression of MMP-21 is uniquely controlled by Pax and Notch transcription factors known to be critical for organogenesis. MMP-21 is transiently expressed in mouse embryogenesis and elevated in embryonic neuronal tissues. Our observations clearly indicate that there is an important specific function for MMP-21 in embryogenesis, and, especially, in neuronal cells.