AIMP3单倍剂量不足会破坏癌基因诱导的p53激活和基因组稳定性。

AIMP3 haploinsufficiency disrupts oncogene-induced p53 activation and genomic stability.

作者信息

Park Bum-Joon, Oh Young Sun, Park Seung Yong, Choi So Jung, Rudolph Cornelia, Schlegelberger Brigitte, Kim Sunghoon

机构信息

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.

出版信息

Cancer Res. 2006 Jul 15;66(14):6913-8. doi: 10.1158/0008-5472.CAN-05-3740.

DOI:10.1158/0008-5472.CAN-05-3740

PMID:16849534

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.

摘要

AIMP3（以前称为p18）已被证明在DNA损伤反应中上调p53。在此，我们表明AIMP3将致癌应激与p53激活联系起来以防止细胞转化。AIMP3的单等位基因缺失以及AIMP3的抑制可阻断生长因子或Ras依赖的p53诱导。AIMP3杂合细胞对单独由Ras或Myc等癌基因诱导的细胞转化变得敏感。转化的AIMP3+/-细胞在细胞分裂和染色体结构上表现出严重异常。因此，AIMP3通过ATM和ATR的差异激活在p53介导的针对致癌应激的肿瘤抑制反应中以及在维持基因组稳定性方面发挥关键作用。