Bifunctional effects of a protein kinase inhibitor (H-7) on heat-induced p53-dependent WAF1 accumulation

Experimental Cell Research
X WangT Ohnishi

Abstract

We have previously shown that heat shock induces p53-dependent WAF1 expression. To understand the role of protein kinases in the heat-induced p53-mediated signal transduction pathway, the effects of H-7, a serine/threonine kinase inhibitor, on WAF1 accumulation were investigated using two human glioblastoma cell lines differing in p53 status or their transfectants with various p53-expression vectors. Unexpectedly, H-7 alone induced p53-dependent WAF1 accumulation with a biphasic pattern depending on H-7 dose; i.e., low doses of H-7 induced the accumulation of both p53 and WAF1, whereas, a high dose of H-7 induced p53 but no WAF1 accumulation, suggesting that p53 accumulation and p53-dependent WAF1 expression are separable. Heat shock and H-7 induce p53-dependent WAF1 accumulation through different pathways as shown in A-172 cells stably expressing a temperature-sensitive mutant p53. However, our results show that these two pathways cross-talk with each other in the combined treatment of H-7 and heat shock studies. These findings indicate that inhibition of protein kinases can act as a novel stress to evoke the p53 pathway and that p53 activation by heat shock requires activation of yet unidentified protein kinases in vivo. The ...Continue Reading

Citations

Feb 22, 2001·Radiation Research·H MatsumotoE Kano
Jul 4, 1998·International Journal of Radiation Oncology, Biology, Physics·H MatsumotoE Kano
Sep 7, 2001·Advances in Space Research : the Official Journal of the Committee on Space Research (COSPAR)·T OhnishiS Nagaoka

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