title: Mutational analysis of Max: role of basic, helix-loop-helix/leucine zipper domains in DNA binding, dimerization and regulation of Myc-mediated transcriptional activation.
abstract: The Max protein forms a heterodimeric complex with the Myc family of proteins and binds to DNA in a sequence-specific manner. We investigated the role of the helix-loop-helix (HLH), leucine zipper (LZ) and basic domains of Max in protein complex formation, DNA-binding activity and transcriptional regulation. We mutagenized the basic, HLH and LZ domains of Max and studied the ability of the normal and mutant proteins to bind to DNA as both homo- and heterodimers and their ability to heterodimerize with Myc. Helix-1 and helix-2 regions of Max were found to be critical for homodimer formation and subsequent DNA binding, while the LZ was essential for heterodimer formation. In transient transfection assays the Myc protein functioned as a transcriptional activator while Max protein repressed the trans-activation observed with Myc.
authors.affiliation: Fels Institute for Cancer Research and Molecular Biology, Philadelphia, Pennsylvania 19140.
authors.forename: C D
authors.initials: CD
authors.lastname: Reddy
authors.forename: P
authors.initials: P
authors.lastname: Dasgupta
authors.forename: P
authors.initials: P
authors.lastname: Saikumar
authors.forename: H
authors.initials: H
authors.lastname: Dudek
authors.forename: F J
authors.initials: FJ
authors.lastname: Rauscher
authors.forename: E P
authors.initials: EP
authors.lastname: Reddy
mesh_terms: D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D012097:Repressor Proteins; D013329:Structure-Activity Relationship; D014157:Transcription Factors; D015533:Transcriptional Activation
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499330:MAX protein, human; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA