Repression by the Mad(Mxi1)-Sin3 complex.
The functions of Myc in transformation and transactivation are countered by the suppressive actions of the Mad(Mxi1) family. Mad(Mxi1) proteins not only compete with Myc for dimerization to Max and binding to Myc/Max consensus sites but also recruit powerful repressors of gene expression. A prediction of the yin-yang relationship between Myc and Mad(Mxi1) families would be that the latter constitutes a new class of tumor suppressors. Here, we review the current literature on the Mad(Mxi1) family, with particular attention paid to the molecular mechanisms by which these proteins antagonize the actions of Myc in normal and neoplastic cells.
Schreiber-Agus
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Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. agus@aecom.yu.edu
DePinho
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D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D001665:Binding Sites; D001667:Binding, Competitive; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002843:Chromatin / Q000235:genetics; D016384:Consensus Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology*; D019281:Dimerization; D005057:Eukaryotic Cells / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006655:Histone Deacetylases; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D005810:Multigene Family; D009369:Neoplasms / Q000235:genetics; D009687:Nuclear Proteins / Q000502:physiology; D056971:Nuclear Receptor Co-Repressor 1; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors*; D012097:Repressor Proteins / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*; D025521:Tumor Suppressor Proteins
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D050976:Basic-Leucine Zipper Transcription Factors; D002843:Chromatin; D004268:DNA-Binding Proteins; D006655:Histone Deacetylases; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C079439:MXD1 protein, human; C079440:MXI1 protein, human; C499479:Mad protein, mouse; C512788:Mxi1 protein, mouse; C067850:Myc associated factor X; C539127:NCOR1 protein, human; C539128:Ncor1 protein, mouse; C071731:SIN3 protein, S cerevisiae; C068422:Max protein, mouse