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J Biol Chem. 1996 Apr 12;271(15):8593-8.

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

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Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo 112, Japan.


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.

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