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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.

SUBMITTER: Stead MA

PROVIDER: S-EPMC4259219 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Structures of heterodimeric POZ domains of Miz1/BCL6 and Miz1/NAC1.

Stead Mark Alexander MA Wright Stephanie Claire SC

Acta crystallographica. Section F, Structural biology communications 20141114 Pt 12

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 NAC ...[more]

PMID: 25484205

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