A novel function for HSF1-induced mitotic exit failure and genomic instability through direct interaction between HSF1 and Cdc20
- 3 December 2007
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 27 (21), 2999-3009
- https://doi.org/10.1038/sj.onc.1210966
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.Keywords
This publication has 16 references indexed in Scilit:
- Selective suppression of lymphomas by functional loss of Hsf1 in a p53-deficient mouse model for spontaneous tumorsOncogene, 2007
- A New Perspective on Tumor Endothelial Cells: Unexpected Chromosome and Centrosome AbnormalitiesCancer Research, 2005
- Induction of HSF1 expression is associated with sporadic colorectal cancerWorld Journal of Gastroenterology, 2004
- Two Redundant Oscillatory Mechanisms in the Yeast Cell CycleDevelopmental Cell, 2003
- Roles of the heat shock transcription factors in regulation of the heat shock response and beyondThe FASEB Journal, 2001
- Long-term prognostic significance of HSP-70, c-myc and HLA-DR expression in patients with malignant melanomaEuropean Journal of Surgical Oncology, 2001
- A Novel Association between the Human Heat Shock Transcription Factor 1 (HSF1) and Prostate AdenocarcinomaThe American Journal of Pathology, 2000
- Mutations of mitotic checkpoint genes in human cancersNature, 1998
- Genetic instability in colorectal cancersNature, 1997
- Correlation between synthesis of heat shock proteins and development of thermotolerance in Chinese hamster fibroblasts.Proceedings of the National Academy of Sciences of the United States of America, 1982