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Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) is an enzyme that promotes tumor cell invasion in tissues. Although the proteolytic activity of MT1-MMP is indispensable for invasion, it is also regulated by functions of the cytoplasmic tail. In this study we obtained a new human gene whose product binds to the tail sequence in yeast. The product, MTCBP-1, is a 19-kDa protein that belongs to the newly proposed Cupin superfamily composed of proteins with diverse functions. MTCBP-1 expressed in cells formed a complex with MT1-MMP and co-localized at the membrane. It was also detected in both the cytoplasm and nucleus, where MT1-MMP does not exist. In human tumor cell lines MTCBP-1 expression was significantly low compared with non-transformed fibroblasts, and enforced expression of MTCBP-1 inhibited the activity of MT1-MMP in promoting cell migration and invasion. MTCBP-1 showed significant homology to the bacterial aci-reductone dioxygenase, which is an enzyme in methionine metabolism. The C-terminal part of MTCBP-1 is identical to Sip-L, which is reported to be important for human hepatitis C virus replication. Thus, MTCBP-1 may have multiple functions other than the regulation of MT1-MMP, which presumably depends on the subcellular compartment.

Original publication




Journal article


The Journal of biological chemistry

Publication Date





12734 - 12743


Division of Cancer Cell Research, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.


Cell Line, COS Cells, Cell Line, Tumor, Cell Membrane, Cell Nucleus, Cytoplasm, Subcellular Fractions, Fibroblasts, Animals, Humans, Neoplasm Invasiveness, Collagen, Metalloendopeptidases, Dioxygenases, Proteoglycans, Peptides, Carrier Proteins, Laminin, Tumor Suppressor Proteins, Recombinant Proteins, DNA, Complementary, RNA, Messenger, Drug Combinations, Microscopy, Fluorescence, Fluorescent Antibody Technique, Indirect, Blotting, Western, Precipitin Tests, Blotting, Northern, Two-Hybrid System Techniques, Transfection, Reverse Transcriptase Polymerase Chain Reaction, Cell Movement, Down-Regulation, Gene Expression Regulation, Neoplastic, Amino Acid Sequence, Base Sequence, Protein Structure, Tertiary, Sequence Homology, Amino Acid, Multigene Family, Open Reading Frames, Plasmids, Molecular Sequence Data, Matrix Metalloproteinases, Membrane-Associated