DNA damage response involves modulation of Ku70 and Rb functions by cyclin A1 in leukemia cells

Ping Ji, Nicole Bäumer, Taijun Yin, Sven Diederichs, Feng Zhang, Carmela Beger, Karl Welte, Simone Fulda, Wolfgang E. Berdel, Hubert Serve, Carsten Müller-Tidow

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Cyclin A1 plays a critical role in hematopoietic malignancies, notably, acute myeloid leukemia. The molecular mechanisms of cyclin A1 action are incompletely understood. Here, we show that cyclin A1 functions are mediated by the retinoblastoma and the Ku70 pathway. High levels of cyclin A1 and the associated CDK2 kinase activity were associated with increasing levels of phosphorylated retinoblastoma in vivo. UV irradiation induced a switch of the CDK2 towards cyclin A1, with accordance to changes in CDK2 kinase activity. The C-terminus of cyclin A1 directly interacted with Ku70, and DNA binding activity of Ku70 was modulated by cyclin A1/ CDK2 and phosphatase treatment. Cyclin A1-deficiency induced by shRNA increased apoptosis that is induced by DNA damage and death receptor ligands. Taken together, these analyses demonstrate that cyclin A1 exerts antiapoptotic functions by interacting with retinoblastoma and Ku proteins in leukemia cells.

Original languageEnglish (US)
Pages (from-to)706-713
Number of pages8
JournalInternational Journal of Cancer
Volume121
Issue number4
DOIs
StatePublished - Aug 15 2007
Externally publishedYes

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Keywords

  • Apoptosis
  • Cell cycle control
  • Cyclin A1
  • DNA repair

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ji, P., Bäumer, N., Yin, T., Diederichs, S., Zhang, F., Beger, C., Welte, K., Fulda, S., Berdel, W. E., Serve, H., & Müller-Tidow, C. (2007). DNA damage response involves modulation of Ku70 and Rb functions by cyclin A1 in leukemia cells. International Journal of Cancer, 121(4), 706-713. https://doi.org/10.1002/ijc.22634