Regulation of Pim-1 by Hsp90.
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.
Division of Molecular Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka, 565-0871, Japan.
K
K
Mizuno
T
T
Shirogane
A
A
Shinohara
A
A
Iwamatsu
M
M
Hibi
T
T
Hirano
D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D050822:Cytokine Receptor gp130; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051573:Proto-Oncogene Proteins c-pim-1; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D017931:DNA Primers; D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1