title: 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.
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.
authors.affiliation: Department of Biochemistry, College of Medicine, Hallym University, Chuncheon, Gangwon-do 200-702, South Korea.
authors.forename: Jee-In
authors.initials: JI
authors.lastname: Heo
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Oh
authors.forename: Yoon-Jung
authors.initials: YJ
authors.lastname: Kho
authors.forename: Jeong-Hyeon
authors.initials: JH
authors.lastname: Kim
authors.forename: Hong-Joon
authors.initials: HJ
authors.lastname: Kang
authors.forename: Seong-Hoon
authors.initials: SH
authors.lastname: Park
authors.forename: Hyun-Seok
authors.initials: HS
authors.lastname: Kim
authors.forename: Jong-Yeon
authors.initials: JY
authors.lastname: Shin
authors.forename: Min-Ju
authors.initials: MJ
authors.lastname: Kim
authors.forename: Minju
authors.initials: M
authors.lastname: Kim
authors.forename: Sung Chan
authors.initials: SC
authors.lastname: Kim
authors.forename: Jae-Bong
authors.initials: JB
authors.lastname: Park
authors.forename: Jaebong
authors.initials: J
authors.lastname: Kim
authors.forename: Jae-Yong
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D051379:Mice; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D048490:raf Kinases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D016283:Proto-Oncogene Proteins p21(ras)