Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Amino Acid Sequence
-
Animals
-
Base Sequence
-
Blotting, Northern
-
Blotting, Western
-
COS Cells
-
Carrier Proteins / chemistry*
-
Carrier Proteins / physiology*
-
Cell Line
-
Cell Line, Tumor
-
Cell Membrane / metabolism
-
Cell Movement
-
Cell Nucleus / metabolism
-
Collagen / pharmacology
-
Cytoplasm / enzymology*
-
Cytoplasm / metabolism
-
DNA, Complementary / metabolism
-
Dioxygenases
-
Down-Regulation*
-
Drug Combinations
-
Fibroblasts / metabolism
-
Fluorescent Antibody Technique, Indirect
-
Gene Expression Regulation, Neoplastic*
-
Humans
-
Laminin / pharmacology
-
Matrix Metalloproteinases, Membrane-Associated
-
Metalloendopeptidases / metabolism
-
Metalloendopeptidases / physiology*
-
Microscopy, Fluorescence
-
Molecular Sequence Data
-
Multigene Family
-
Neoplasm Invasiveness
-
Open Reading Frames
-
Peptides / chemistry
-
Plasmids / metabolism
-
Precipitin Tests
-
Protein Structure, Tertiary
-
Proteoglycans / pharmacology
-
RNA, Messenger / metabolism
-
Recombinant Proteins / chemistry
-
Reverse Transcriptase Polymerase Chain Reaction
-
Sequence Homology, Amino Acid
-
Subcellular Fractions
-
Transfection
-
Tumor Suppressor Proteins / chemistry
-
Two-Hybrid System Techniques
Substances
-
Carrier Proteins
-
DNA, Complementary
-
Drug Combinations
-
Laminin
-
Peptides
-
Proteoglycans
-
RNA, Messenger
-
Recombinant Proteins
-
Tumor Suppressor Proteins
-
matrigel
-
Collagen
-
ADI1 protein, human
-
Dioxygenases
-
Matrix Metalloproteinases, Membrane-Associated
-
Metalloendopeptidases