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.
