title: TCTP directly regulates ATM activity to control genome stability and organ development in Drosophila melanogaster.
abstract: Translationally controlled tumour protein (TCTP) is implicated in growth regulation and cancer. Recently, human TCTP has been suggested to play a role in the DNA damage response by forming a complex with ataxia telangiectasia-mutated (ATM) kinase . However, the exact nature of this interaction and its roles in vivo remained unclear. Here, we utilize Drosophila as an animal model to study the nuclear function of Drosophila TCTP (dTCTP). dTCTP mutants show increased radiation sensitivity during development as well as strong genetic interaction with dATM mutations, resulting in severe defects in developmental timing, organ size and chromosome stability. We identify Drosophila ATM (dATM) as a direct binding partner of dTCTP and describe a mechanistic basis for dATM activation by dTCTP. Altogether, this study provides the first in vivo evidence for direct modulation of dATM activity by dTCTP in the control of genome stability and organ development.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
authors.forename: Sung-Tae
authors.initials: ST
authors.lastname: Hong
authors.affiliation: 1] Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea [2] Graduate School of Nanoscience and Technology, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseong-gu, Daejeon 305-701, Korea.
authors.forename: Kwang-Wook
authors.initials: KW
authors.lastname: Choi
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002453:Cell Cycle; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D016195:G2 Phase; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D005982:Glutathione Transferase / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases; D034622:RNA Interference; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D014408:Biomarkers, Tumor; D002843:Chromatin; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C517693:TCTP protein, Drosophila; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D005982:Glutathione Transferase; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; C514947:Tefu protein, Drosophila