MM-1, a c-Myc-binding protein, is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer.
The c-myc oncogene product (c-Myc) is a transcription factor that dimerizes with Max and recognizes the E-box sequence, and it plays key functions in cell proliferation, differentiation, and apoptosis. We previously showed that MM-1 bound to myc box II within the transactivation domain of c-Myc and repressed the E-box-dependent transcriptional ... activity of c-Myc. Here we report that MM-1 showed features of a tumor suppressor. In an EST data base search for cDNAs homologous to MM-1, we found a frequent substitution of amino acid 157 of MM-1, from alanine to arginine (A157R), and the substitution was observed more in tumor cells than in normal cells. A survey of the A157R mutation of MM-1 in 57 cultured cancer cells and 90 tissues from cancer patients showed that the A157R was present in about 50-60% of leukemia/lymphoma cells and in more than 75% of squamous cell carcinoma of tongue cancer. Although both the A157R and the wild-type MM-1 bound to c-Myc, only A157R lost the activities to repress both the E-box-dependent transcriptional activity of c-Myc and the myc/ras cooperative transforming activity in rat 3Y1 cells. Furthermore, the wild-type MM-1, but not A157R, arrested the growth of 3Y1 cells. The human MM-1 gene was mapped at chromosome 12q12-12q13, where many chromosome abnormalities in cancer cells have been reported. The results suggest that MM-1 is a novel candidate for a tumor suppressor that controls the transcriptional activity of c-Myc.
Mesh Terms:
3T3 Cells, Amino Acids, Animals, Blotting, Northern, Cell Cycle, Cell Division, Cell Line, Chromosomes, Human, Pair 12, Cloning, Molecular, DNA, DNA, Complementary, Exons, Expressed Sequence Tags, Fluorescent Antibody Technique, Indirect, Hela Cells, Humans, In Situ Hybridization, Fluorescence, Leukemia, Luciferases, Lymphoma, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Plasmids, Protein Binding, Protein Structure, Tertiary, Rats, Repressor Proteins, Time Factors, Tongue Neoplasms, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured
3T3 Cells, Amino Acids, Animals, Blotting, Northern, Cell Cycle, Cell Division, Cell Line, Chromosomes, Human, Pair 12, Cloning, Molecular, DNA, DNA, Complementary, Exons, Expressed Sequence Tags, Fluorescent Antibody Technique, Indirect, Hela Cells, Humans, In Situ Hybridization, Fluorescence, Leukemia, Luciferases, Lymphoma, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Mutation, Plasmids, Protein Binding, Protein Structure, Tertiary, Rats, Repressor Proteins, Time Factors, Tongue Neoplasms, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Transfection, Tumor Cells, Cultured
J. Biol. Chem.
Date: Nov. 30, 2001
PubMed ID: 11567024
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