Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein-1 is a new member of the Cupin superfamily. A possible multifunctional protein acting as an invasion suppressor down-regulated in tumors.

Journal article

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.

Authors: Uekita, T; Gotoh, I; Kinoshita, T; Itoh, Y; Sato, H

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 279
• Issue: 13
• Pages: 12734-12743
• Publication date: 2004-03-01
• DOI: 10.1074/jbc.m309957200
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Animals; Cell Nucleus; Sequence Homology, Amino Acid; Fluorescent Antibody Technique, Indirect; DNA, Complementary; Reverse Transcriptase Polymerase Chain Reaction; Cell Membrane; Open Reading Frames; Transfection; Two-Hybrid System Techniques; Gene Expression Regulation, Neoplastic; Metalloendopeptidases; Cell Line; COS Cells; Proteoglycans; Multigene Family; Fibroblasts; Collagen; Recombinant Proteins; Plasmids; Base Sequence; Drug Combinations; Blotting, Western; Cytoplasm; Cell Movement; Peptides; Amino Acid Sequence; Molecular Sequence Data; Neoplasm Invasiveness; Down-Regulation; Laminin; Subcellular Fractions; Humans; Matrix Metalloproteinases, Membrane-Associated; Cell Line, Tumor; Tumor Suppressor Proteins; Carrier Proteins; Precipitin Tests; Protein Structure, Tertiary; Dioxygenases; Blotting, Northern; RNA, Messenger; Microscopy, Fluorescence