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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

DOI

10.1074/jbc.M309957200

Type

Journal article

Journal

J biol chem

Publication Date

26/03/2004

Volume

279

Pages

12734 - 12743

Keywords

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