Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc.
C-myc, a member of the basic helix-loop-helix-leucine zipper (bHLH-ZIP) protein family activates target genes in heterodimeric association with another bHLH-ZIP protein, Max. Max readily homodimerizes, competes with C-myc-Max heterodimers, and represses transcription. Four additional bHLH-ZIP proteins, Mad1, Mxi1, Mad3 and Mad4, heterodimerize with Max and also repress transcription of c-myc-responsive ... genes. We employed a yeast two-hybid approach to identify proteins which interact with Mxi. We identified a novel ZIP-containing protein, Mmip1 (Mad member-interacting protein 1) that strongly dimerizes with all four Mad members, but not with c-myc, Max, or with unrelated HLH proteins. The Mmip1-Mxi association is mediated by the ZIP domain of each polypeptide and is as strong or stronger than the associations between c-myc and Max or Max and Mxi1. In vitro, Mmip1 can inhibit DNA binding by Max-Mad heterodimers and, in vivo, can reverse the suppressive effects of Mad proteins on c-myc functions. Mmipl is found in a variety of cells types, is induced by serum stimulation, and can be co-immunoprecipitated from fibroblasts in association with Mxi1. By interfering with the dimerization between Max and Mad family member proteins, Mmip1 can indirectly up-regulate the transcriptional activity of c-myc and suppress the antiproliferative actions of Mad proteins.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, Cell Cycle Proteins, Cell Line, Cercopithecus aethiops, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Fibroblasts, Genes, myc, Helix-Loop-Helix Motifs, Humans, Leucine Zippers, Molecular Sequence Data, Polymerase Chain Reaction, Proteochondroitin Sulfates, Proto-Oncogene Proteins c-myc, Recombinant Proteins, Repressor Proteins, Transcription Factors, Transfection, Tumor Suppressor Proteins
Amino Acid Sequence, Animals, Base Sequence, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Basic Helix-Loop-Helix Transcription Factors, Cell Cycle Proteins, Cell Line, Cercopithecus aethiops, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Fibroblasts, Genes, myc, Helix-Loop-Helix Motifs, Humans, Leucine Zippers, Molecular Sequence Data, Polymerase Chain Reaction, Proteochondroitin Sulfates, Proto-Oncogene Proteins c-myc, Recombinant Proteins, Repressor Proteins, Transcription Factors, Transfection, Tumor Suppressor Proteins
Oncogene
Date: Mar. 05, 1998
PubMed ID: 9528857
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