Zinc finger and BTB domain-containing protein 25 (ZBTB25)

Zinc finger and BTB domain-containing protein 25 (ZBTB25) is a transcriptional repressor belonging to the broad complex, tram track, bric-a-brac/poxvirus and zinc finger (BTB/POZ) family of transcription factors[1]. It contains a DNA-binding zinc finger motif at its C-terminus and a protein-binding BTB/POZ domain at the N-terminus, mediating both protein–DNA and protein–protein interactions[1]. ZBTB25 forms part of corepressor complexes, such as those with histone deacetylase 1 (HDAC1) and Sin3a, to actively repress transcription at specific gene promoters—particularly interleukin-12B (IL-12B)—with important roles in immune regulation during infection (e.g., *Mycobacterium tuberculosis*)[1]. Suppression of ZBTB25 derepresses immune gene expression and induces autophagy, providing a rationale for its pursuit as a host-directed therapy target in tuberculosis[1]. It also interacts with viral polymerase complexes, such as the influenza A viral RNA-dependent RNA polymerase (RdRp), where it enhances viral RNA synthesis and suppresses the host interferon response, making it a potential target for antiviral intervention[2]. Compounds such as disulfiram and specialized zinc-ejectors (e.g., DP) can inactivate ZBTB25 by targeting its zinc finger domain, inhibiting its function and disrupting its roles in infection and viral replication[1][2]. Members of the ZBTB family, including ZBTB25, have broader implications in cancer and immune disease due to their general epigenetic and immune regulatory activities[1].

Other names

C14orf51KUPZNF46Zinc finger protein 46Zinc finger protein KUP

Zinc finger domain ejection/inhibition (loss of protein function via zinc removal), Inhibition of transcriptional repression, Interference with protein–protein and protein–nucleic acid interactions