title: AIMP3 haploinsufficiency disrupts oncogene-induced p53 activation and genomic stability.
abstract: AIMP3 (previously known as p18) was shown to up-regulate p53 in response to DNA damage. Here, we show that AIMP3 couples oncogenic stresses to p53 activation to prevent cell transformation. Growth factor- or Ras-dependent induction of p53 was blocked by single allelic loss of AIMP3 as well as by suppression of AIMP3. AIMP3 heterozygous cells became susceptible to cell transformation induced by oncogenes such as Ras or Myc alone. The transformed AIMP3+/- cells showed severe abnormality in cell division and chromosomal structure. Thus, AIMP3 plays crucial roles in p53-mediated tumor-suppressive response against oncogenic stresses via differential activation of ATM and ATR, and in the maintenance of genomic stability.
authors.affiliation: National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul, Korea and Institute for Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany.
authors.forename: Bum-Joon
authors.initials: BJ
authors.lastname: Park
authors.forename: Young Sun
authors.initials: YS
authors.lastname: Oh
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Park
authors.forename: So Jung
authors.initials: SJ
authors.lastname: Choi
authors.forename: Cornelia
authors.initials: C
authors.lastname: Rudolph
authors.forename: Brigitte
authors.initials: B
authors.lastname: Schlegelberger
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
mesh_terms: D000483:Alleles; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian; D005347:Fibroblasts; D005786:Gene Expression Regulation / Q000235:genetics*; D011905:Genes, ras; D042822:Genomic Instability / Q000235:genetics*; D051379:Mice; D016372:RNA, Antisense / Q000235:genetics; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D050763:Cyclin-Dependent Kinase Inhibitor p18; D016372:RNA, Antisense; D016159:Tumor Suppressor Protein p53