Ku80 is required but not sufficient for Galpha13-mediated endodermal differentiation in P19 embryonic carcinoma cells

Biochemical and Biophysical Research Communications
Jyotshnabala KanungoC C Malbon

Abstract

We have shown that a constitutively active Galpha13 (Galpha13Q226L) 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 Galpha13Q226L. 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 Galpha13Q226L and an antisense Ku80 abrogated the retarded growth rate and endodermal differentiation observed in cells expressing only Galpha13Q226L. Overexpression of Galpha13Q226L 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 Galpha13-mediated endodermal differentiation in P19 cells.

References

Dec 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·A DvirW S Dynan
Jul 15, 1985·European Journal of Biochemistry·F A JacobsB H Sells
Dec 1, 1983·Molecular and Cellular Biology·E M Jones-VilleneuveM W McBurney
Aug 1, 1982·The Journal of Cell Biology·E M Jones-VilleneuveV I Kalnins
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·P Labhart
Sep 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·D E LarsonL I Rothblum
Sep 20, 1993·FEBS Letters·H JiangM I Simon
Feb 1, 1993·Molecular and Cellular Biology·A M ChanS A Aaronson
Jan 10, 1997·Biochemical Pharmacology·C C Malbon
Dec 1, 1996·The Journal of Steroid Biochemistry and Molecular Biology·R L KablerA H Cavanaugh
Jul 1, 1997·Arthritis and Rheumatism·J WangW H Reeves
Aug 15, 1997·The EMBO Journal·G R FangerG L Johnson
Apr 16, 1998·Biochemistry·T L Jones, J S Gutkind
Aug 14, 1998·Molecular Cell·G C LiC Cordon-Cardo
Nov 9, 2001·The Journal of Biological Chemistry·Hsien-yu WangCraig C Malbon
Jan 18, 2003·Biological Chemistry·Theologos M Michaelidis, Ingrid Grummt

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Citations

Aug 13, 2011·Molecular and Cellular Biochemistry·Jyotshnabala Kanungo, Settara C Chandrasekharappa
Apr 10, 2013·Alzheimer's Research & Therapy·Jyotshna Kanungo

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