> Details

Węsierska‐Gądek, Józefa; Gueorguieva, Marieta; Kramer, Matthias P.; Ranftler, Carmen; Sarg, Bettina; Lindner, Herbert

A new, unexpected action of olomoucine, a CDK inhibitor, on normal human cells: Up‐regulation of CLIMP‐63, a cytoskeleton‐linking membrane protein

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: A new, unexpected action of olomoucine, a CDK inhibitor, on normal human cells: Up‐regulation of CLIMP‐63, a cytoskeleton‐linking membrane protein
  • Contributor: Węsierska‐Gądek, Józefa; Gueorguieva, Marieta; Kramer, Matthias P.; Ranftler, Carmen; Sarg, Bettina; Lindner, Herbert
  • imprint: Wiley, 2007
  • Published in: Journal of Cellular Biochemistry
  • Language: English
  • DOI: 10.1002/jcb.21596
  • ISSN: 0730-2312; 1097-4644
  • Keywords: Cell Biology ; Molecular Biology ; Biochemistry
  • Origination:
  • Footnote:
  • Description: <jats:title>Abstract</jats:title><jats:p>Inhibition of cyclin‐dependent kinases (CDKs) is a novel strategy in the therapy of human malignancies. The pharmacological CDK inhibitors representing a few distinct classes of compounds exert different target specificity. Considering the fact that dividing and quiescent cells differ in their CDK activity and in the pattern of their expression, one might expect that anti‐proliferative efficiency of the pharmacological CDK inhibitors would depend on the mitotic index of treated cells. The present article shows that olomoucine (OLO), a weak CDK2 inhibitor has new, unexpected activity. At concentrations up to 100 µM OLO did not inhibit proliferation of normal human cells, but arrested growth of human HL‐60 leukemia cells. The anti‐proliferative effect of OLO was clearly weaker than that of roscovitine (ROSC). Surprisingly, OLO at low doses strongly up‐regulated a cellular protein with approximately 65 kDa in normal, but not in immortalized and cancer cells. By mass spectrometric analysis CLIMP‐63, a cytoskeleton‐linking membrane protein was identified as the major component of the up‐regulated protein band. These results were subsequently confirmed by immunoblotting. Further experiments revealed that OLO, but not ROSC, strongly up‐regulates CLIMP‐63 in a dose‐ and time‐dependent manner solely in senescent cells. J. Cell. Biochem. 102: 1405–1419, 2007. © 2007 Wiley‐Liss, Inc.</jats:p>