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Regulation of Pim-1 by Hsp90
K Mizuno1, T Shirogane, A Shinohara
1Division of Molecular Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
Abstract:
The protooncogene Pim-1 encodes serine/threonine protein kinases that are involved in cytokine-mediated cell proliferation and in lymphoma- and leukemogenesis. It is largely unknown how Pim-1 executes its biological effects. Here we show that Pim-1 physically interacts with heat shock protein 90 alpha and beta (Hsp90alpha and beta). The Hsp90-specific inhibitor geldanamycin (GA) induced a rapid degradation of Pim-1 and reduced its kinase activity. The expression of Hsp90alpha was regulated by a signal from the cytokine receptor gp130, as is Pim-1's expression. These results indicate that Hsp90 is coordinately regulated with Pim-1 and is involved in the stabilization and function of Pim-1.