title: Relationship between ATM and ribosomal protein S6 revealed by the chemical inhibition of Ser/Thr protein phosphatase type 1.
abstract: The optimal cellular responses to DNA damage are modulated by kinase and phosphatase. The ataxia telangiectasia mutated (ATM) is a Ser/Thr kinase which is the core of the DNA damage signaling apparatus. The Ser/Thr protein phosphatase type 1 (PP1) inhibitor, tautomycetin (TC) and an antibody to the phospho-(S/T)Q sites of the ATM substrate were used to identify the common substrates for PP1 and ATM in regulating the pathway for DNA damage response. Ribosomal protein S6 (RPS6) was first identified as a substrate for PP1 and ATM. The phosphorylation at Ser247 of RPS6 was then significantly decreased by PP1-mediated dephosphorylation immediately after UV irradiation. These results suggest that PP1 specifically dephosphorylated RPS6 at phospho-Ser247 in vivo. In response to DNA damage, ATM activity was finally required for the phosphorylation of RPS6 at Ser247. We propose from these results a novel mechanism for modulating the RPS6 function by PP1 and ATM which regulates cell growth and survival in response to DNA-damage stimuli.
authors.affiliation: Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo, Japan.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Shinya
authors.initials: S
authors.lastname: Mitsuhashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ikejo
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kawamura
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Makoto
authors.initials: M
authors.lastname: Ubukata
mesh_terms: D020816:Amino Acid Motifs; D000918:Antibody Specificity; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005663:Furans / Q000494:pharmacology; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000494:pharmacology; D008958:Models, Molecular; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D011487:Protein Conformation; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D038601:Ribosomal Protein S6 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005663:Furans; D008055:Lipids; D038601:Ribosomal Protein S6; D025521:Tumor Suppressor Proteins; C058744:tautomycetin; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D054645:Protein Phosphatase 1