The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium

Abstract

Through the specific binding of a negative calcium-responsive element to its binding protein in response to extracellular Ca (Ca2+(e)), negative calcium-responsive element-bearing genes, such as the human parathyroid hormone gene, are negatively regulated by Ca2+(e). The Ku antigen mediated negative gene regulation by Ca2+(e) by interacting with a redox factor protein, REF1. Although sequence-nonspecific DNA binding activity of the Ku antigen has been well characterized, the mechanism of its sequence-specific DNA binding remained obscure. Here, we report that the specific binding of the Ku antigen to another protein, REF1, leads to DNA-protein complex formation with a novel sequence specificity and thereby regulates gene expression.