A novel function for HSF1-induced mitotic exit failure and genomic instability through direct interaction between HSF1 and Cdc20

Oncogene. 2008 May 8;27(21):2999-3009. doi: 10.1038/sj.onc.1210966. Epub 2007 Dec 3.


Although heat-shock factor (HSF) 1 is a known transcriptional factor of heat-shock proteins, other pathways like production of aneuploidy and increased protein stability of cyclin B1 have been proposed. In the present study, the regulatory domain of HSF1 (amino-acid sequence 212-380) was found to interact directly with the amino-acid sequence 106-171 of Cdc20. The association between HSF1 and Cdc20 inhibited the interaction between Cdc27 and Cdc20, the phosphorylation of Cdc27 and the ubiquitination activity of anaphase-promoting complex (APC). The overexpression of HSF1 inhibited mitotic exit and the degradations of cyclin B1 and securin, which resulted in production of aneuploidy and multinucleated cells, but regulatory domain-deficient HSF1 did not. Moreover, HSF1-overexpressing cells showed elevated levels of micronuclei and genomic alteration. The depletion of HSF1 from cells highly expressing HSF1 reduced nocodazole-mediated aneuploidy in cells. These findings suggest a novel function of HSF1 frequently overexpressed in cancer cells, to inhibit APC/C activity by interacting with Cdc20, and to result in aneuploidy development and genomic instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Animals
  • Cdc20 Proteins
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cells, Cultured
  • DNA-Binding Proteins / metabolism
  • DNA-Binding Proteins / physiology*
  • Genes, APC
  • Heat Shock Transcription Factors
  • Humans
  • Mice
  • Mitosis / physiology*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • Cdc20 Proteins
  • Cdc20 protein, mouse
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Heat Shock Transcription Factors
  • Hsf1 protein, mouse
  • Transcription Factors