Hypergravity induces phosphorylation of p53 at serine 15, but not an expression of p53-downstream genes.
We investigated the p53 signaling pathway induced by hypergravity in the human glioblastoma cell line A172. Hypergravity (20 x g) induced the accumulation of p53 and the phosphorylation of p53 at Ser-15. The phosphorylation of p53 with hypergravity was not inhibited by wortmannin, the PI3-kinase inhibitor. This indicated that the p53 signal pathway induced by hypergravity is different from other p53 signal pathways, such as that of the DNA damage signal. Hypergravity did not induce an expression of the genes Waf-1 or Bax, located downstream from p53. We also examined the expression of genes with hypergravity by using a DNA microarray containing oligo DNA from 30,000 human genes. Hypergravity (20 x g, 6 h) did induce the expression of some genes concerned with the cell signaling pathway and cytoskeleton of the cell, but not any of the p53-downstream genes. DNA microarray revealed the induction of many genes to enable the cells to adapt to the hypergravity environment.
Okaichi
Kumio
K
Department of Radiation Biophysics, Radiation Effect Research Unit, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. okaichi@net.nagasaki-u.ac.jp
Ide
Miwa
M
Usui
Aya
A
Okumura
Yutaka
Y
D000595:Amino Acid Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015870:Gene Expression; D006801:Humans; D018471:Hypergravity; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein