THAP domain containing 12 (THAP12)

THAP domain containing 12 (THAP12) is a member of the THAP family of zinc finger DNA-binding proteins, characterized by an N-terminal C2CH-type THAP domain that recognizes DNA[1][3][4]. THAP12 forms a nuclear complex with the zinc finger protein ZFP574, supporting the G1-to-S-phase transition in the cell cycle, and is essential for both normal and malignant lymphocyte survival[1]. Depletion or deletion of THAP12 (or ZFP574) leads to cell cycle arrest and impaired hematopoiesis, with a potent suppressive effect on B cell leukemia and lymphoma in mouse models[1]. THAP12 also plays roles in type I interferon signaling and can act as an indirect activator of the interferon-induced serine/threonine protein kinase PKR, thereby participating in cellular antiviral and apoptotic responses[1]. There are no well-characterized drugs known to target THAP12 directly, but the ZFP574–THAP12 complex has been proposed as a novel therapeutic target in B cell malignancies. Safety concerns include risks to normal hematopoiesis and cytopenias if the complex is targeted broadly.

Other names

THAP domain containing 12death-associated protein 4P58IPK-regulatory protein52 kDa repressor of the inhibitor of the protein kinaseDAP4P52rIPKPRKRIRTHAP0p52rIPKp58IPK-interacting protein58 kDa interferon-induced protein kinase-interacting proteintesticular tissue protein Li 133

Inhibition or disruption leads to cell cycle arrest and impaired cell proliferation, especially in lymphocytes and leukemic B cells[1]