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TCTP directly regulates ATM activity to control genome stability and organ development in Drosophila melanogaster

Sung-Tae Hong1, Kwang-Wook Choi2

  • 1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.

Nature Communications
|December 20, 2013
PubMed

Insights

Translationally controlled tumor protein (TCTP) directly modulates ATM kinase activity, crucial for DNA damage response and genome stability. This study reveals TCTP

Area of Science:

  • Cell Biology
  • Genetics
  • Molecular Biology

Background:

  • Translationally controlled tumor protein (TCTP) is involved in cell growth and cancer.
  • Previous research suggested a role for human TCTP in DNA damage response via interaction with ATM kinase, but in vivo evidence was lacking.

Purpose of the Study:

  • To investigate the in vivo nuclear function of Drosophila TCTP (dTCTP).
  • To elucidate the interaction between dTCTP and Drosophila ATM (dATM) and its role in DNA damage response and development.

Main Methods:

  • Utilized Drosophila as an animal model.
  • Generated dTCTP mutants and studied their interaction with dATM mutations.
  • Investigated genetic interactions, radiation sensitivity, developmental defects, and chromosome stability.

Main Results:

  • dTCTP mutants exhibited increased radiation sensitivity and severe developmental defects when combined with dATM mutations.
  • Identified dATM as a direct binding partner of dTCTP.
  • Elucidated a mechanism for dATM activation by dTCTP.

Conclusions:

  • This study provides the first in vivo evidence of dTCTP directly modulating dATM activity.
  • dTCTP plays a critical role in controlling genome stability and organ development through its interaction with dATM.

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