The interaction between Ku antigen and REF1 protein mediates negative gene regulation by extracellular calcium.
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.
Chung
U
U
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Bunkyo-ku, Tokyo 112, Japan.
Igarashi
T
T
Nishishita
T
T
Iwanari
H
H
Iwamatsu
A
A
Suwa
A
A
Mimori
T
T
Hata
K
K
Ebisu
S
S
Ogata
E
E
Fujita
T
T
Okazaki
T
T
D000595:Amino Acid Sequence; D034961:Antigens, Nuclear; D001483:Base Sequence; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism*; D019757:Carbon-Oxygen Lyases; D004265:DNA Helicases; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D012097:Repressor Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D019757:Carbon-Oxygen Lyases; D000072200:Ku Autoantigen; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D002118:Calcium