Daxx regulates mitotic progression and prostate cancer predisposition
Data(s) |
01/04/2013
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Resumo |
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. |
Formato |
application/pdf |
Identificador | |
Publicador |
Oxford University Press |
Relação |
http://eprints.qut.edu.au/64991/1/64991_submitted.pdf DOI:10.1093/carcin/bgs391 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. http://purl.org/au-research/grants/NHMRC/1031228 http://purl.org/au-research/grants/NHMRC/1031221 |
Fonte |
School of Biomedical Sciences; Faculty of Health; Institute of Health and Biomedical Innovation |
Palavras-Chave | #111201 Cancer Cell Biology #111203 Cancer Genetics #Daxx #Mitotic progression #Prostate Cancer #Predisposition #Gleason score #metastasis #epithelial cell lines |
Tipo |
Journal Article |