ZBRK1 is a member of the Kruppel-associated box-zinc finger protein (KRAB-ZFP) protein family of transcriptional repressors. ZBRK1 has been shown to not only be up-regulated in senescent fibroblasts but also interacts with BRCA1, a transcriptional regulator with tumor suppressor activity. ZBRK1 binds to a specific sequence within the GADD45 gene, supporting the assembly of a nuclear complex containing BRCA1 and repressing its transcription. Recent experiments demonstrate that ZBRK1 can homo-oligomerize in vitro and in vivo through a C-terminal transcriptional repression domain (CTRD), and this oligomerization facilitates the ZBRK1-directed transcriptional repression through ZBRK1 response elements. These results suggest that higher order ZBRK1 oligomers may assemble through both protein-DNA and CTRD-dependent protein-protein interactions.
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