The Cys2-His2 Zinc Finger Domains of Juxtaposed with Another Zinc Finger Protein 1 (JAZF1) Are Important for the Vitamin K Dependent JAZF1-Bak1 Interaction and Subcellular Localization of JAZF1

Vitamin K2 (VK2) exerts potent anticancer activity through the induction of apoptosis. This process is mediated by the covalent attachment of VK2 epoxide metabolite, VK2-O, to Bcl-2 antagonist killer 1 (Bak1), a post-translational modification termed “VK2ation,” which activates the mitochondrial apoptotic pathway. In a previous study, we demonstrated that Juxtaposed with Another Zinc Finger Protein 1 (JAZF1) is a critical mediator of Bak1 VK2ation and subsequent VK2-induced apoptosis. JAZF1 contains three Cys2-His2 zinc finger (ZnF) motifs essential for protein-protein interactions. In this study, we verified whether these ZnFs mutations affected JAZF1-Bak1 interaction. According to analysis of protein-protein interaction, we identified the first and third ZnFs as the motifs required for a VK2-O-dependent JAZF1-Bak1 interaction. Moreover, we found that these ZnFs are necessary for VK2ation of Bak1. The observation of the intracellular localization of JAZF1 suggested that the disruption of zinc finger structure may affect the intracellular localization. In conclusion, we clarified that the first and third ZnFs of JAZF1 have an important role in VK2ation of Bak1. Further studies on VK2ation such as this study may lead to clarifying a new function of vitamin K2 as an active type of vitamin K in tissue.