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Molecular Biology Reports

, Volume 39, Issue 8, pp 8007–8014 | Cite as

ATM mediates interdependent activation of p53 and ERK through formation of a ternary complex with p-p53 and p-ERK in response to DNA damage

  • Jee-In Heo
  • Soo-Jin Oh
  • Yoon-Jung Kho
  • Jeong-Hyeon Kim
  • Hong-Joon Kang
  • Seong-Hoon Park
  • Hyun-Seok Kim
  • Jong-Yeon Shin
  • Min-Ju Kim
  • Minju Kim
  • Sung Chan Kim
  • Jae-Bong Park
  • Jaebong Kim
  • Jae-Yong Lee
Article

Abstract

DNA damage in eukaryotic cells induces signaling pathways mediated by the ATM, p53 and ERK proteins, but the interactions between these pathways are not completely known. To address this issue, we performed a time course analysis in human embryonic fibroblast cells treated with DNA-damaging agents. DNA damage induced the phosphorylation of p53 at Ser 15 (p-p53) and the phosphorylation of ERK (p-ERK). Inhibition of p53 by a dominant negative mutant or in p53−/− fibroblast cells abolished ERK phosphorylation. ERK inhibitor prevented p53 phosphorylation, indicating that phosphorylations of p53 and p-ERK are interdependent each other. A time course analysis showed that ATM interacted with p-p53 and p-ERK in early time (0.5 h) and interaction between ATM-bound p-p53 and p-ERK or ATM-bound p-ERK and p-p53 occurred in late time (3 h) of DNA damage. These results indicate that ATM mediates interdependent activation of p53 and ERK through formation of a ternary complex between p-p53 and p-ERK in response to DNA damage to cause growth arrest.

Keywords

ATM ERK p53 Etoposide Cisplatin Camptothecin 

Notes

Acknowledgments

This work was supported partly by Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0030750). This work was also supported partly by a grant of “Human Resource Development Center for Economic Region Leading Industry” directed by the Ministry of Education, Science & Technology (MEST) and the National Research Foundation of Korea (NRF).

Supplementary material

11033_2012_1647_MOESM1_ESM.doc (482 kb)
Supplementary material 1 (DOC 482 kb)

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Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Jee-In Heo
    • 1
    • 2
  • Soo-Jin Oh
    • 1
  • Yoon-Jung Kho
    • 2
  • Jeong-Hyeon Kim
    • 1
  • Hong-Joon Kang
    • 7
  • Seong-Hoon Park
    • 3
    • 4
  • Hyun-Seok Kim
    • 8
  • Jong-Yeon Shin
    • 5
  • Min-Ju Kim
    • 6
  • Minju Kim
    • 1
  • Sung Chan Kim
    • 1
  • Jae-Bong Park
    • 1
  • Jaebong Kim
    • 1
  • Jae-Yong Lee
    • 1
    • 2
  1. 1.Department of Biochemistry, College of MedicineHallym UniversityChuncheonSouth Korea
  2. 2.Institute of Natural Medicine, College of MedicineHallym UniversityChuncheonSouth Korea
  3. 3.Department of Radiation OncologyVanderbilt UniversityNashvilleUSA
  4. 4.Department of PediatricsVanderbilt UniversityNashvilleUSA
  5. 5.Genomic Medicine Institute, Medical Research CenterSeoul National UniversitySeoulSouth Korea
  6. 6.Department of Anatomy and Neurobiology, College of MedicineHallym UniversityChuncheonSouth Korea
  7. 7.Genetic Disease Research Section, NIDDKNational Institutes of HealthBethesdaUSA
  8. 8.Department of Life Science, College of Natural Science Ewha Womans UniversitySeoulSouth Korea

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