title: B-myc: N-terminal recognition of myc binding proteins.
abstract: B-Myc is an endogenous, N-terminal homologue of transcription factor c-Myc that lacks the C-terminal DNA binding and protein dimerization domain of c-Myc. Clinical mutations in the c-Myc N-terminal region, and the subsequent misregulation of Myc, are implicated in the development of numerous human cancers. Myc functions to both activate and repress transcription by associating with multiple binding partners. We investigated the structural and dynamical properties of B-Myc, free or associated with the transactivation inhibitor, MM-1, and the activator, TBP, using NMR spectroscopy. B-Myc has no persistent tertiary structure, yet regions corresponding to Myc homology boxes 1 and 2 (MBI and MBII, respectively) have molten globule-like characteristics. B-Myc binds to MM-1 in a specific manner without becoming highly structured. The local regions of B-Myc involved in binding differ for MM-1 and TBP, and regions not identified by mutagenesis are found to be involved in MM-1 binding. The results provide new insights into Myc N-terminal protein-protein interactions. We propose a model for Myc regulation through differential involvement of MBI and MBII in the binding of Myc interacting proteins.
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907-2091, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Burton
authors.forename: Sampo
authors.initials: S
authors.lastname: Mattila
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Taparowsky
authors.forename: Carol Beth
authors.initials: CB
authors.lastname: Post
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D011485:Protein Binding; D021381:Protein Transport; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: C431443:Bmyc protein, mouse; D016271:Proto-Oncogene Proteins c-myc