Pim-1 kinase stability is regulated by heat shock proteins and the ubiquitin-proteasome pathway

K Petersen Shay, Z Wang, P Xing, IFC McKenzie… - Molecular cancer …, 2005 - AACR
K Petersen Shay, Z Wang, P Xing, IFC McKenzie, NS Magnuson
Molecular cancer research, 2005AACR
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 …
Abstract
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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