DNA-PK phosphorylation sites on Oct-1 promote cell survival following DNA damage.

Octamer transcription factor-1 (Oct-1) has recently been shown to function as a stress sensor that promotes cell survival subsequent to DNA damage. Here, we show that the survival signal imparted by Oct-1 following exposure to ionizing radiation (IR) is dependent upon DNA-dependent protein kinase (DNA-PK)-dependent phosphorylation of a cluster of ...
13 specific ser/thr residues within the N-terminal transcriptional regulatory domain of Oct-1. Although IR treatment did not affect the recruitment of Oct-1 to the histone H2B promoter, the recruitment of RNA polymerase II, TATA-binding protein and histone H4 acetylation were strongly reduced, consistent with a decrease in Oct-1 transcriptional regulatory potential following IR exposure. Ser/Thr-Ala substitution of 13 sites present in Oct-1 transcriptional regulatory domain eliminated Oct-1 phosphorylation subsequent to IR exposure. Further, these substitutions prevented Oct-1 from rescuing the survival of IR-treated Oct-1-/- murine embryonic fibroblasts, providing a direct link between DNA-PK-dependent phosphorylation and the contribution of Oct-1 to cell survival. These results implicate Oct-1 as a primary effector in a DNA-PK-dependent cell survival pathway that is activated by double-stranded DNA breaks.
Mesh Terms:
3T3 Cells, Amino Acid Sequence, Amino Acid Substitution, Animals, Binding Sites, Blotting, Western, Cell Line, Cell Line, Tumor, Cell Survival, DNA Damage, DNA-Activated Protein Kinase, Dose-Response Relationship, Radiation, Histones, Humans, Mice, Mice, Knockout, Molecular Sequence Data, Octamer Transcription Factor-1, Phosphorylation, Promoter Regions, Genetic, Protein Binding, Serine, Threonine, Transfection
Oncogene
Date: Jun. 07, 2007
Download Curated Data For This Publication
104094
Switch View:
  • Interactions 2