title: Both the helix-loop-helix and the leucine zipper motifs of c-Myc contribute to its dimerization specificity with Max.
abstract: The oncoprotein c-Myc contains two dimerization motifs- the helix-loop-helix (HLH) and the leucine zipper (LZ) - through which c-Myc specifically dimerizes with Max. We substituted regions of the c-Myc HLH and LZ motifs with the corresponding regions of structurally related proteins that do not interact with Max. Specific association of c-Myc with Max was dictated by helices 1 and 2 of the HLH motif and by the LZ. Within helix 2, residues 6 and 7 were important determinants of dimerization specificity. c-Myc and Max proteins with three amino acids inserted between their HLH and LZ motifs interacted efficiently, suggesting that the spacing between the motifs can be varied. Furthermore, alignment of the motifs at the primary sequence level was not obligatory, since Max with the three amino acid insertion could interact with wild-type c-Myc. These findings are consistent with our recently proposed model for the architecture of HLH/LZ domains.
authors.affiliation: Department of Cancer Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: L J
authors.initials: LJ
authors.lastname: Davis
authors.forename: T D
authors.initials: TD
authors.lastname: Halazonetis
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry*; D016350:Leucine Zippers; D008969:Molecular Sequence Data; D009154:Mutation; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry*; D051381:Rats; D014157:Transcription Factors
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; C499329:Max protein, rat; C067850:Myc associated factor X; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D004247:DNA