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Apoptosis

, Volume 14, Issue 5, pp 699–710 | Cite as

Nuclear translocation of dihydrofolate reductase is not a pre-requisite for DNA damage induced apoptosis

  • Ting-Ting Yuan
  • Ying Huang
  • Ci-Xiang Zhou
  • Yun Yu
  • Li-Shun Wang
  • Han-Yi Zhuang
  • Guo-Qiang Chen
Original paper

Abstract

Dihydrofolate reductase (DHFR) is a key enzyme for the synthesis of thymidylate, and therefore, of DNA. By applying subcellular proteomic analysis, we identified that the DHFR protein was translocated from cytoplasm into the nucleus when apoptosis was induced by NSC606985, a camptothecin analogue. The nuclear translocation of DHFR protein during apoptosis was independent of the cellular context, but it was more sensitive in cell death induction by DNA damaging agents such as doxorubicin, etoposide and ultraviolent radiation than endoplasmic reticulum stressors (brefeldin-A and tunicamycin) and anti-microtubule agents (paclitaxel and nocodozole). The addition of methotrexate almost completely blocked the nuclear translocation of DHFR protein. Further investigations showed that the nuclear translocation of DHFR was not a pre-requisite for DNA damage induced apoptosis. Therefore, its potential biological significance remains to be further explored.

Keywords

DHFR Apoptosis Nuclear translocation DNA damage 

Notes

Acknowledgments

We thank Dr. Wei CHEN in Beijing Institute of Microbiology and Epidemiology for generously providing us CHO/dhfr cell line. This work was supported in part by grants from Ministry of Science and Technology (NO2009CB918404), National Natural Science Foundation of China (30630034, 30500216), Chinese Academy of Sciences (KSCX2-YW-R-097) and Science and Technology Commission of Shanghai. T. T. Yuan is a PhD candidate at SIBS and this work is submitted in partial fulfillment of the requirement for the PhD. Dr. G. Q. Chen is a Chang Jiang Scholar of Ministry of Education of People’s Republic of China and is supported by Shanghai Ling-Jun Talent Program.

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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Ting-Ting Yuan
    • 1
  • Ying Huang
    • 2
  • Ci-Xiang Zhou
    • 1
  • Yun Yu
    • 2
  • Li-Shun Wang
    • 2
  • Han-Yi Zhuang
    • 2
  • Guo-Qiang Chen
    • 1
    • 2
  1. 1.Institute of Health ScienceShanghai Institutes for Biological Sciences (SIBS) of Chinese Academy of Sciences and Shanghai Jiao-Tong University School of Medicine (SJTU-SM)ShanghaiChina
  2. 2.Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationSJTU-SMShanghaiChina

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