The transcription regulatory function of p53 was analyzed by using two inducible p53 systems in the human lung cancer cell line H1299. cDNA probes derived from RNA harvested 12 h after p53 induction were used to probe filters containing cDNA arrays. Over 20 genes were found to be significantly induced or suppressed by p53. The induced genes can be classified mainly as cell cycle inhibitors like p21waf, GADD45, apoptosis-related genes like Fas/APO1 and PIG3 or DNA repair genes like DDB2, DNA ligase and G/T mismatch DNA glycosylase. The suppressed genes include mainly cell cycle regulators like cyclin B1, cyclin H and kinases like c-abl, CLK1 and others. The most notable induced gene was MIC-1, encoding a TGF-β-related secretory protein, suggesting a potential paracrine component for p53 growth suppression. (C) 2000 Federation of European Biochemical Societies.
|Number of pages||6|
|State||Published - 17 Mar 2000|
Bibliographical noteFunding Information:
This work was supported in part by Yad Abraham Research Center for Cancer Diagnosis and Therapy and the Rich Foundation for Leukemia Research. G.R. holds the Gregorio and Dora Shapiro Chair for Hematologic Malignancies, Sackler School of Medicine, Tel Aviv University. We thank Drs. A. Hochberg and A. Suhail from The Hebrew University, Jerusalem, Israel, for helpful discussions concerning array image analysis and Dr. M. Oren for p53Val135 expressing H1299 cells.
- DNA array
- DNA repair