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

Oncogene volume 27, pages 2999–3009 (2008)Cite this article

Abstract

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.

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Acknowledgements

This work was supported by the Korean Science and Engineering Foundation (KOSEF) and by the Korean Ministry of Science and Technology (MOST), through the National Nuclear Technology Program.

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Authors and Affiliations

  1. Division of Radiation Effect, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea

    Y J Lee, H J Lee, C M Kang, S Bae & Y S Lee

  2. Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Korea

    J S Lee & S J Lee

  3. College of Natural Sciences, Kangwon National University, Chunchon, Korea

    D Jeoung

  4. Korea Basic Science Institute, Chunchon Center, Chunchon, Korea

    S H Kwon & D Kang

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Correspondence to Y S Lee.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Lee, Y., Lee, H., Lee, J. et al. A novel function for HSF1-induced mitotic exit failure and genomic instability through direct interaction between HSF1 and Cdc20. Oncogene 27, 2999–3009 (2008). https://doi.org/10.1038/sj.onc.1210966

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