BTB/POZ Family

BTB/POZ family members refer to proteins containing the BTB/POZ domain, which is a highly conserved protein-protein interaction domain typically located at the N-terminus of proteins. The core of this domain consists of β-sheets (β1-β4) and α-helices (α1-α5) and can associate with C2H2 zinc fingers, Kelch domains, MATH domains, and other structures to form multiprotein complexes.
BTB/POZ family members perform diverse functions, including transcriptional regulation, chromatin remodeling, protein degradation, and ion channel regulation. They are involved in the ubiquitin-proteasome degradation pathway, where the Cullin3-E3 ubiquitin ligase complex recruits substrate proteins for ubiquitination via the BTB domain. Additionally, BTB/POZ proteins play crucial roles in immune regulation, cell cycle control, and apoptosis. For example, in the ZBTB family, the BTB/POZ domain interacts with co-repressors such as NCOR, BCOR, and SMRT, thereby regulating gene expression.
Dysregulation of BTB/POZ family members is associated with various cancers, including diffuse large B-cell lymphoma (DLBCL), leukemia, and breast cancer. Moreover, these proteins are implicated in neurodegenerative disorders and immune-related diseases, highlighting their significance as potential therapeutic targets^[1].