AIMP3 haploinsufficiency disrupts oncogene-induced p53 activation and genomic stability.
Cancer Res
; 66(14): 6913-8, 2006 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-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.
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Base de dados:
MEDLINE
Assunto principal:
Transformação Celular Neoplásica
/
Regulação da Expressão Gênica
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Proteína Supressora de Tumor p53
/
Genes ras
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Instabilidade Genômica
/
Inibidor de Quinase Dependente de Ciclina p18
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Alemanha