Ku80 is required but not sufficient for Gα13-mediated endodermal differentiation in P19 embryonic carcinoma cells

Abstract

We have shown that a constitutively active G α13 (G α13Q226L) induces differentiation in P19 embryonic carcinoma cells to an endodermal phenotype. In this report, we demonstrate that Ku, a heterodimer of p80 (Ku80) and p70 (Ku70), is upregulated in P19 cells overexpressing G α13Q226L. Ku is the regulatory subunit of the DNA-dependent protein kinase and is primarily involved in DNA repair and recombination. Ku80 also is a somatostatin receptor. We show that while overexpression of Ku80 drastically reduced P19 cell proliferation, it was not sufficient to induce endodermal differentiation. However, coexpression of G α13Q226L and an antisense Ku80 abrogated the retarded growth rate and endodermal differentiation observed in cells expressing only G α13Q226L. Overexpression of G α13Q226L or Ku80 downregulated RNA polymerase I-mediated transcriptional activity and overexpression of antisense Ku80 restored the activity to control level. These results suggest that Ku80 is required for Gα13-mediated endodermal differentiation in P19 cells.