FK228 inhibits Hsp90 chaperone function in K562 cells via hyperacetylation of Hsp70

Biochem Biophys Res Commun. 2007 May 18;356(4):998-1003. doi: 10.1016/j.bbrc.2007.03.076. Epub 2007 Mar 22.


Some pan-histone-deacetylase (HDAC) inhibitors have recently been reported to exert their anti-leukemia effect by inhibiting the activity of class IIB HDAC6, which is the deacetylase of Hsp90 and alpha-tubulin, thereby leading to hyperacetylation of Hsp90, disruption of its chaperone function and apoptosis. In this study, we compared the effect of a class I HDAC inhibitor FK228 with the pan-HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) on the Hsp90 chaperone function of K562 cells. We demonstrated that, although having a weaker inhibitory effect on HDAC6, FK228 mediated a similar disruption of Hsp90 chaperone function compared to SAHA. Unlike SAHA, FK228 did not mediate hyperacetylation of Hsp90, instead the acetylation of Hsp70 was increased and Bcr-Abl was increasingly associated with Hsp70 rather than Hsp90, forming an unstable complex that promotes Bcr-Abl degradation. These results indicated that FK228 may disrupt the function of Hsp90 indirectly through acetylation of Hsp70 and inhibition of its function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Antibiotics, Antineoplastic / administration & dosage
  • Depsipeptides / administration & dosage*
  • Dose-Response Relationship, Drug
  • HSP70 Heat-Shock Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / metabolism*
  • Humans
  • K562 Cells
  • Molecular Chaperones / metabolism


  • Antibiotics, Antineoplastic
  • Depsipeptides
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Molecular Chaperones
  • romidepsin