title: Structures of heterodimeric POZ domains of Miz1/BCL6 and Miz1/NAC1.
abstract: The POZ domain is an evolutionarily conserved protein-protein interaction domain that is found in approximately 40 mammalian transcription factors. POZ domains mediate both homodimerization and the heteromeric interactions of different POZ-domain transcription factors with each other. Miz1 is a POZ-domain transcription factor that regulates cell-cycle arrest and DNA-damage responses. The activities of Miz1 are altered by its interaction with the POZ-domain transcriptional repressors BCL6 and NAC1, and these interactions have been implicated in tumourigenesis in B-cell lymphomas and in ovarian serous carcinomas that overexpress BCL6 and NAC1, respectively. A strategy for the purification of tethered POZ domains that form forced heterodimers is described, and crystal structures of the heterodimeric POZ domains of Miz1/BCL6 and of Miz1/NAC1 are reported. These structures will be relevant for the design of therapeutics that target POZ-domain interaction interfaces.
authors.affiliation: School of Biology, University of Leeds, Leeds LS2 9JT, England.
authors.forename: Mark Alexander
authors.initials: MA
authors.lastname: Stead
authors.affiliation: School of Biology, University of Leeds, Leeds LS2 9JT, England.
authors.forename: Stephanie Claire
authors.initials: SC
authors.lastname: Wright
mesh_terms: D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry*; D019281:Dimerization; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000737:chemistry*; D009363:Neoplasm Proteins / Q000737:chemistry*; D011487:Protein Conformation; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins / Q000737:chemistry*
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; C516477:NACC1 protein, human; D009363:Neoplasm Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D012097:Repressor Proteins; C107961:ZBTB17 protein, human
keywords: BTB domain; Miz1/BCL6; Miz1/NAC1; forced heterodimer; tethered heterodimer; transcriptional repressor