title: MM-1, a c-Myc-binding protein, is a candidate for a tumor suppressor in leukemia/lymphoma and tongue cancer.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Department of Pathology, Graduate School of Medicine, College of Medical Technology, Hokkaido University, Kita-ku, Sapporo 060-8012, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujioka
authors.forename: T
authors.initials: T
authors.lastname: Taira
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Nishihara
authors.forename: S M
authors.initials: SM
authors.lastname: Iguchi-Ariga
authors.forename: K
authors.initials: K
authors.lastname: Nagashima
authors.forename: H
authors.initials: H
authors.lastname: Ariga
mesh_terms: D016475:3T3 Cells; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D015152:Blotting, Northern; D002453:Cell Cycle; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002881:Chromosomes, Human, Pair 12; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D020224:Expressed Sequence Tags; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007938:Leukemia / Q000235:genetics / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism* / Q000502:physiology*; D013997:Time Factors; D014062:Tongue Neoplasms / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000596:Amino Acids; D018076:DNA, Complementary; C115636:PFDN5 protein, human; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D008156:Luciferases