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Biotech / Medical : Kosan BioSciences -- KOSN -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (433)	3/31/2005 2:32:37 PM
From: tuck	Read Replies (1) \| Respond to of 933

[Geldanamycin + Bortezomib versus leukemia] >>Mol Cancer Res. 2005 Mar;3(3):170-81. Pim-1 kinase stability is regulated by heat shock proteins and the ubiquitin-proteasome pathway. Petersen Shay K, Wang Z, Xing PX, McKenzie IF, Magnuson NS. School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234. magnuson@wsu.edu. 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.<< The study Rick posted that I'm responding to involved breast cancer cells. Cheers, Tuck