Involvement of the ubiquitin pathway in decreasing Ku70 levels in response to drug-induced apoptosis

Vivian Gama, Tomoyuki Yoshida, Jose A. Gomez, David P. Basile, Lindsey D. Mayo, Arthur L. Haas, Shigemi Matsuyama

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Ku70 plays an important role in DNA damage repair and prevention of cell death. Previously, we reported that apoptosis caused a decrease in cellular Ku70 levels. In this study, we analyzed the mechanism of how Ku70 levels decrease during drug-induced apoptosis. In HeLa cells, staurosporin (STS) caused a decrease in Ku70 levels without significantly affecting Ku70 mRNA levels. We found that Ku70 protein was highly ubiquitinated in various cell types, such as HeLa, HEK293T, Dami (a megakaryocytic cell line), endothelial, and rat kidney cells. An increase in ubiquitinated Ku70 protein was observed in apoptotic cells, and proteasome inhibitors attenuated the decrease in Ku70 levels in apoptotic cells. These results suggest that the ubiquitin-proteasome proteolytic pathway plays a role in decreasing Ku70 levels in apoptotic cells. Ku70 forms a heterodimer with Ku80, which is required for the DNA repair activity of Ku proteins. We also found that Ku80 levels decreased in apoptotic cells and that Ku80 is a target of ubiquitin. Ubiquitinated Ku70 was not found in the Ku70-Ku80 heterodimer, suggesting that modification by ubiquitin inhibits Ku heterodimer formation. We propose that the ubiquitin-dependent modification of Ku70 plays an important role in the control of cellular levels of Ku70.

Original languageEnglish (US)
Pages (from-to)488-499
Number of pages12
JournalExperimental Cell Research
Volume312
Issue number4
DOIs
StatePublished - Feb 15 2006

Keywords

  • Apoptosis
  • Bax
  • DNA-PK
  • Ku70
  • Ku80
  • Ubiquitination

ASJC Scopus subject areas

  • Cell Biology

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