The ZBTB family of proteins is comprised of diverse zinc finger proteins that also contain a BTB (BR-C, ttk and bab) domain. Similar to Kaiso, a zinc-finger containing protein that can bind methylated CpGs, ZBTB4 can also bind methylated DNA and repress transcription. ZBTB4 has been shown to associate with the Sin3/histone deacetylase co-repressor and repress expression of P21CIP1 as part of a heterodimeric complex with Miz1. In cultured cells, depletion of ZBTB4 promotes cell cycle arrest in response to p53 activation and suppresses apoptosis through regulation of P21CIP1, suggesting that ZBTB4 is a critical determinant of the cellular response to p53 activation. HIPK2, a kinase that is involved in cellular proliferation and survival, phosphorylates and down-regulates ZBTB4 under normal cell growth conditions; this degradation increases with DNA damage.
KAISO-L1; KAISO-like zinc finger protein 1; Zinc finger and BTB domain-containing protein 4