Profile of gene expression regulated by induced p53: connection to the TGF-beta family

The transcription regulatory function of p53 was analyzed by using two indu cible p53 systems in the human lung cancer cell line H1299, cDNA probes der ived from RNA harvested 12 h after p53 induction were used to probe filters containing cDNA arrays. Over 20 genes were found to be significantly induc ed or suppressed by p53, The induced genes can be classified mainly as cell cycle inhibitors like p21waf, GADD45, apoptosis-related genes like Fas/APO 1 and PIG3 or DNA repair genes like DDB2, DNA ligase and GIT mismatch DNA g lycosylase, The suppressed genes include mainly cell cycle regulators like cyclin B1, cyclin H and kinases like c-ab1, CLK1 and others. The most notab le induced gene was MIC-1, encoding a TGF-beta-related secretory protein, s uggesting a potential paracriue component for p53 growth suppression. (C) 2 000 Federation of European Biochemical Societies.