Heat shock protein 90 regulates the metaphase-anaphase transition in a polo-like kinase-dependent manner.
We have shown previously that the molecular chaperone heat shock protein 90 (Hsp90) is required for a proper centrosome function. Indeed, this Hsp90 function seems to be reflected in Polo-like kinase stability. Inhibition of Hsp90 in HeLa cells results in cell cycle arrest either in G2 stage or at the metaphase-anaphase transition. Here, we show that this inhibition leads to inactivation of the anaphase-promoting complex or cyclosome by both dephosphorylation and induction of the spindle assembly checkpoint. Hsp90 inhibition compromises two of the main mitotic kinases, Polo-like kinase 1 (Plk1) and cdc2. Interestingly, this mitotic arrest does not occur in certain tumor cell lines where Hsp90 and Plk1 are not associated. Those cells are able to process mitosis successfully and have an active Plk1 despite Hsp90 inactivation. Therefore, it seems that Hsp90 regulates completion of mitosis depending on its association with Plk1.
Molecular Oncology Programme, Centro Nacional de Investigaciones Oncológicas, Melchior Fernandez Almagro 3, 28029 Madrid, Spain. gcarcer@cnio.es
Guillermo
G
de Cárcer
D000705:Anaphase; D016203:CDC2 Protein Kinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D016195:G2 Phase / Q000187:drug effects; D005875:Gibberellins / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008677:Metaphase; D008938:Mitosis; D010766:Phosphorylation / Q000187:drug effects; D010937:Plant Growth Regulators / Q000494:pharmacology; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D008941:Spindle Apparatus / Q000502:physiology*; D000097869:Polo-Like Kinase 1
D016203:CDC2 Protein Kinase; D018797:Cell Cycle Proteins; D005875:Gibberellins; D018841:HSP90 Heat-Shock Proteins; D010937:Plant Growth Regulators; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D000097869:Polo-Like Kinase 1; C007842:gibberellic acid