RRC ID 43754
著者 Li Y, Mitsuhashi S, Ikejo M, Miura N, Kawamura T, Hamakubo T, Ubukata M.
タイトル Relationship between ATM and ribosomal protein S6 revealed by the chemical inhibition of Ser/Thr protein phosphatase type 1.
ジャーナル Biosci Biotechnol Biochem
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.
巻・号 76(3)
ページ 486-94
公開日 2012-1-1
DOI 10.1271/bbb.110774
PII JST.JSTAGE/bbb/110774
PMID 22451389
MeSH Amino Acid Motifs Antibody Specificity Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins / metabolism* DNA Damage DNA-Binding Proteins / metabolism* Enzyme Inhibitors / pharmacology* Furans / pharmacology HEK293 Cells HeLa Cells Humans Lipids / pharmacology Models, Molecular Phosphorylation / drug effects Phosphorylation / radiation effects Protein Conformation Protein Phosphatase 1 / antagonists & inhibitors* Protein Phosphatase 1 / chemistry Protein Phosphatase 1 / immunology Protein Phosphatase 1 / metabolism* Protein Serine-Threonine Kinases / metabolism* Ribosomal Protein S6 / metabolism* Signal Transduction / drug effects Signal Transduction / radiation effects Tumor Suppressor Proteins / metabolism* Ultraviolet Rays
IF 1.516
引用数 9
WOS 分野 FOOD SCIENCE & TECHNOLOGY BIOTECHNOLOGY & APPLIED MICROBIOLOGY CHEMISTRY, APPLIED BIOCHEMISTRY & MOLECULAR BIOLOGY
リソース情報
ヒト・動物細胞 HeLa(RCB0007) 293T(RCB2202)