title: Sin3 corepressor function in Myc-induced transcription and transformation.
abstract: Many basic-helix-loop-helix-leucine zipper (b-HLH-LZ) proteins, including the Myc family and non-Myc family, bind a common DNA sequence CACGTG, yet have quite different biological actions. Myc binds this sequence as a heterodimer with Max in the activation of both transcription and transformation. The Myc family members Mad and Mxi1 are known to suppress Myc-induced transcription and transformation and to dimerize with Max to form ternary complexes with the mammalian Sin3 transcriptional corepressor (mSin3). The b-HLH-LZ domain of TFEB, which cannot heterodimerize within the Myc family, does not suppress Myc-induced transcription or transformation. However, transfer of a 25- to 36-aa region from Mad or Mxi1, which interacts with mSin3, to the b-HLH-LZ of TFEB, mediated profound suppression of Myc-induced transcription and transformation. These results suggest that the DNA binding specificities of the Myc family and non-Myc family b-HLH-LZ proteins, in the context of the cellular genes involved in Myc-induced transformation, are shared. The results also demonstrate that targeting mSin3 to CACGTG sites via a non-Myc family DNA binding domain is sufficient to oppose Myc activity in growth regulation.
authors.affiliation: Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Harper
authors.forename: Y
authors.initials: Y
authors.lastname: Qiu
authors.forename: P A
authors.initials: PA
authors.lastname: Sharp
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D018257:Helix-Loop-Helix Motifs; D006655:Histone Deacetylases; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D006655:Histone Deacetylases; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C079440:MXI1 protein, human; C499479:Mad protein, mouse; C512788:Mxi1 protein, mouse; C071731:SIN3 protein, S cerevisiae; C064972:TFEB protein, human