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J.Health Sci., 46(3), 200-203, 2000
Involvement of Stress-Activated MAP Kinase p38 in p53-Independent Induction of p21/WAF1/Cip1 Gene Expression
Kiyoshi Egawa and Kiyoshi Nose*
Department of Microbiology, Showa University School of Pharmaceutical Sciences, Hatanodai 1 -5 -8, Shinagawa-ku, Tokyo 142 -8555, Japan
A p53-independent increase in p21/WAF1/Cip1 gene expression is induced by anti-cancer agents such as trichostatin, actinomycin D and butyrate, and the signaling cascade of this induction was examined in cells stably transformed with a luciferase reporter under transcriptional control of the p21/WAF1/Cip1 gene. An inhibitor of stress-activated protein kinase p38 (SB203580) efficiently inhibited the induction, while PD98059, an inhibitor of MEK1, showed weaker inhibition. The dominant negative form of MKK6 inhibited the transcriptional activation of p21/WAF1/Cip1 gene in transient assay, whereas the dominant negative form of MKK4 did not affect it. Western blotting using antibodies against activated MAP kinases showed that butyrate, trichostatin and actinomycin D activated p38 in p53-defective human osteoblastic cells, but ERK1/2 and JNK activities were not increased significantly by these treatments. These results indicate that p38 kinase is the principal signaling molecule involved in the induction of p21/WAF1/Cip1 gene expression by butyrate, trichostatin and actinomycin D.
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