Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity.
Myc family proteins appear to function through heterodimerization with the stable, constitutively expressed bHLH-Zip protein, Max. To determine whether Max mediates the function of regulatory proteins other than Myc, we screened a lambda gt11 expression library with radiolabeled Max protein. One cDNA identified encodes a new member of the bHLH-Zip protein family, Mad. Human Mad protein homodimerizes poorly but binds Max in vitro, forming a sequence-specific DNA binding complex with properties very similar to those of Myc-Max. Both Myc-Max and Mad-Max heterocomplexes are favored over Max homodimers, and, unlike Max homodimers, the DNA binding activity of the heterodimers is unaffected by CKII phosphorylation. Mad does not associate with Myc or with representative bHLH, bZip, or bHLH-Zip proteins. In vivo transactivation assays suggest that Myc-Max and Mad-Max complexes have opposing functions in transcription and that Max plays a central role in this network of transcription factors.
Ayer
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DE
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Kretzner
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Eisenman
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RN
D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D001667:Binding, Competitive; D047388:Casein Kinases; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016259:Genes, myc; D006801:Humans; D007313:Insecta; D046911:Macromolecular Substances; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism*; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499330:MAX protein, human; C079439:MXD1 protein, human; D046911:Macromolecular Substances; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA; D011494:Protein Kinases; D047388:Casein Kinases