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.
Original language | English |
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Pages (from-to) | 2999-3009 |
Number of pages | 11 |
Journal | Oncogene |
Volume | 27 |
Issue number | 21 |
DOIs | |
State | Published - 8 May 2008 |
Externally published | Yes |
Bibliographical note
Funding Information: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.
Keywords
- Aneuploidy
- HSF1
- Inhibition of APC activity
- Interaction with Cdc20
- Mitotic arrest