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.
|
Authors | Y J Lee, H J Lee, J S Lee, D Jeoung, C M Kang, S Bae, S J Lee, S H Kwon, D Kang, Y S Lee |
Journal | Oncogene
(Oncogene)
Vol. 27
Issue 21
Pg. 2999-3009
(May 08 2008)
ISSN: 1476-5594 [Electronic] England |
PMID | 18059335
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Cdc20 Proteins
- Cdc20 protein, mouse
- Cell Cycle Proteins
- DNA-Binding Proteins
- Heat Shock Transcription Factors
- Hsf1 protein, mouse
- Transcription Factors
|
Topics |
- Aneuploidy
- Animals
- Cdc20 Proteins
- Cell Cycle Proteins
(metabolism)
- Cell Line, Tumor
- Cells, Cultured
- DNA-Binding Proteins
(metabolism, physiology)
- Genes, APC
- Heat Shock Transcription Factors
- Humans
- Mice
- Mitosis
(physiology)
- Transcription Factors
(metabolism, physiology)
|