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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2005-3-30
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pubmed:abstractText |
Elevated expression of the serine/threonine kinase Pim-1 increases the incidence of lymphomas in Pim-1 transgenic mice and has also been found to occur in some human cancers. Pim-1 acts as a cell survival factor and may prevent apoptosis in malignant cells. It was therefore of interest to understand to what extent maintenance and degradation of Pim-1 protein is affected by heat shock proteins (Hsp) and the ubiquitin-proteasome pathway in K562 and BV173 human leukemic cells. The half-life of Pim-1 protein in these cells was found to increase from 1.7 to 3.1 hours when induced by heat shock or by treating the cells with the proteasome inhibitor PS-341 (bortezomib). The Hsp90 inhibitor geldanamycin prevented the stabilization of Pim-1 by heat shock. Using immunoprecipitation, it was determined that Pim-1 is targeted for degradation by ubiquitin and that Hsp70 is associated with Pim-1 under these circumstances. Conversely, Hsp90 was found to protect Pim-1 from proteasomal degradation. A luminescence-based kinase assay showed that Pim-1 kinase bound to Hsp70 or Hsp90 remains active, emphasizing the importance of its overall cellular levels. This study shows how Pim-1 levels can be modulated in cells through degradation and stabilization.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Benzoquinones,
http://linkedlifedata.com/resource/pubmed/chemical/Boronic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/HSP70 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/HSP90 Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lactams, Macrocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/PIM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Pim1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-pim-1,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazines,
http://linkedlifedata.com/resource/pubmed/chemical/Quinones,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/bortezomib,
http://linkedlifedata.com/resource/pubmed/chemical/geldanamycin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1541-7786
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
3
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
170-81
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15798097-Adenosine Triphosphate,
pubmed-meshheading:15798097-Animals,
pubmed-meshheading:15798097-Apoptosis,
pubmed-meshheading:15798097-Benzoquinones,
pubmed-meshheading:15798097-Boronic Acids,
pubmed-meshheading:15798097-Cell Line, Tumor,
pubmed-meshheading:15798097-Electroporation,
pubmed-meshheading:15798097-Flow Cytometry,
pubmed-meshheading:15798097-HSP70 Heat-Shock Proteins,
pubmed-meshheading:15798097-HSP90 Heat-Shock Proteins,
pubmed-meshheading:15798097-Heat-Shock Proteins,
pubmed-meshheading:15798097-Hot Temperature,
pubmed-meshheading:15798097-Humans,
pubmed-meshheading:15798097-Immunoblotting,
pubmed-meshheading:15798097-Immunoprecipitation,
pubmed-meshheading:15798097-K562 Cells,
pubmed-meshheading:15798097-Lactams, Macrocyclic,
pubmed-meshheading:15798097-Mice,
pubmed-meshheading:15798097-Mice, Transgenic,
pubmed-meshheading:15798097-Proteasome Endopeptidase Complex,
pubmed-meshheading:15798097-Protein Binding,
pubmed-meshheading:15798097-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15798097-Proto-Oncogene Proteins,
pubmed-meshheading:15798097-Proto-Oncogene Proteins c-pim-1,
pubmed-meshheading:15798097-Pyrazines,
pubmed-meshheading:15798097-Quinones,
pubmed-meshheading:15798097-Time Factors,
pubmed-meshheading:15798097-Ubiquitin
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pubmed:year |
2005
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pubmed:articleTitle |
Pim-1 kinase stability is regulated by heat shock proteins and the ubiquitin-proteasome pathway.
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pubmed:affiliation |
School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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