The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase.
The Ku antigen (70- and 80-kDa subunits) is a regulatory subunit of DNA-dependent protein kinase (DNA-PK) that promotes the recruitment of the catalytic subunit of DNA-PK (DNA-PKcs) to DNA ends and to specific DNA sequences from which the kinase is activated. Ku and DNA-PKcs plays essential roles in double-stranded DNA ... break repair and V(D)J recombination and have been implicated in the regulation of specific gene transcription. In a yeast two-hybrid screen of a Jurkat T cell cDNA library, we have identified a specific interaction between the 70-kDa subunit of Ku heterodimer and the homeodomain of HOXC4, a homeodomain protein expressed in the hematopoietic system. Unexpectedly, a similar interaction with Ku was observed for several additional homeodomain proteins including octamer transcription factors 1 and 2 and Dlx2, suggesting that specific binding to Ku may be a property shared by many homeodomain proteins. Ku-homeodomain binding was mediated through the extreme C terminus of Ku70 and was abrogated by amino acid substitutions at Lys595/Lys596. Ku binding allowed the recruitment of the homeodomain to DNA ends and dramatically enhanced the phosphorylation of homeodomain-containing proteins by DNA-PK. These results suggest that Ku functions as a substrate docking protein for signaling by DNA-PK to homeodomain proteins from DNA ends.
Mesh Terms:
Adrenocorticotropic Hormone, Amino Acid Sequence, Animals, Antigens, Nuclear, Chickens, Cloning, Molecular, Cricetinae, DNA Helicases, DNA-Activated Protein Kinase, DNA-Binding Proteins, Dimerization, Fungal Proteins, Gene Expression Regulation, Homeodomain Proteins, Humans, Jurkat Cells, Mice, Molecular Sequence Data, Nuclear Proteins, Octamer Transcription Factor-2, Phosphorylation, Protein Binding, Protein Biosynthesis, Protein-Serine-Threonine Kinases, Recombinant Proteins, Saccharomyces cerevisiae Proteins, Sequence Alignment, Sequence Deletion, Sequence Homology, Amino Acid, Ticks, Transcription Factors, Transcription, Genetic, Xenopus
Adrenocorticotropic Hormone, Amino Acid Sequence, Animals, Antigens, Nuclear, Chickens, Cloning, Molecular, Cricetinae, DNA Helicases, DNA-Activated Protein Kinase, DNA-Binding Proteins, Dimerization, Fungal Proteins, Gene Expression Regulation, Homeodomain Proteins, Humans, Jurkat Cells, Mice, Molecular Sequence Data, Nuclear Proteins, Octamer Transcription Factor-2, Phosphorylation, Protein Binding, Protein Biosynthesis, Protein-Serine-Threonine Kinases, Recombinant Proteins, Saccharomyces cerevisiae Proteins, Sequence Alignment, Sequence Deletion, Sequence Homology, Amino Acid, Ticks, Transcription Factors, Transcription, Genetic, Xenopus
J. Biol. Chem.
Date: May. 18, 2001
PubMed ID: 11279128
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