Daxx regulates mitotic progression and prostate cancer predisposition

Kwan, Pak Shing, Lau, Chi Chiu, Chiu, Yung Tuen, Man, Cornelia, Liu, Ji, Tang, Kai Dun, Wong, Yong Chuan, & Ling, Ming-Tat (2013) Daxx regulates mitotic progression and prostate cancer predisposition. Carcinogenesis, 34(4), pp. 750-759.

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Mitotic progression of mammalian cells is tightly regulated by the E3 ubiquitin ligase anaphase promoting complex (APC)/C. Deregulation of APC/C is frequently observed in cancer cells and is suggested to contribute to chromosome instability and cancer predisposition. In this study, we identified Daxx as a novel APC/C inhibitor frequently overexpressed in prostate cancer. Daxx interacts with the APC/C coactivators Cdc20 and Cdh1 in vivo, with the binding of Cdc20 dependent on the consensus destruction boxes near the N-terminal of the Daxx protein. Ectopic expression of Daxx, but not the D-box deleted mutant (DaxxΔD-box), inhibited the degradation of APC/Cdc20 and APC/Cdh1 substrates, leading to a transient delay in mitotic progression. Daxx is frequently upregulated in prostate cancer tissues; the expression level positively correlated with the Gleason score and disease metastasis (P = 0.027 and 0.032, respectively). Furthermore, ectopic expression of Daxx in a non-malignant prostate epithelial cell line induced polyploidy under mitotic stress. Our data suggest that Daxx may function as a novel APC/C inhibitor, which promotes chromosome instability during prostate cancer development.

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ID Code: 64991
Item Type: Journal Article
Refereed: Yes
Keywords: Daxx, Mitotic progression, Prostate Cancer, Predisposition, Gleason score, metastasis, epithelial cell lines
DOI: 10.1093/carcin/bgs391
ISSN: 1460-2180
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Cell Biology (111201)
Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200) > Cancer Genetics (111203)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 02 Dec 2013 23:09
Last Modified: 13 Oct 2015 22:18

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