| USP7 and Daxx regulate mitosis progression and taxane sensitivity by affecting stability of Aurora-A kinase. | |
| | |
MedLine Citation:
|
PMID: 23348568 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
|
A large number of patients are resistant to taxane-based chemotherapy. Functional mitotic checkpoints are essential for taxane sensitivity. Thus, mitotic regulators are potential markers for therapy response and could be targeted for anticancer therapy. In this study, we identified a novel function of ubiquitin (Ub)-specific processing protease-7 (USP7) that interacts and cooperates with protein death domain-associated protein (Daxx) in the regulation of mitosis and taxane resistance. Depletion of USP7 impairs mitotic progression, stabilizes cyclin B and reduces stability of the mitotic E3 Ub ligase, checkpoint with forkhead and Ring-finger (CHFR). Consequently, cells with depleted USP7 accumulate Aurora-A kinase, a CHFR substrate, thus elevating multipolar mitoses. We further show that these effects are independent of the USP7 substrate p53. Thus, USP7 and Daxx are necessary to regulate proper execution of mitosis, partially via regulation of CHFR and Aurora-A kinase stability. Results from colony formation assay, in silico analysis across the NCI60 platform and in breast cancer patients suggest that USP7 levels inversely correlate with response to taxanes, pointing at the USP7 protein as a potential predictive factor for taxane response in cancer patients. In addition, we demonstrated that inhibition of Aurora-A attenuates USP7-mediated taxane resistance, suggesting that combinatorial drug regimens of Taxol and Aurora-A inhibitors may improve the outcome of chemotherapy response in cancer patients resistant to taxane treatment. Finally, our study offers novel insights on USP7 inhibition as cancer therapy.Cell Death and Differentiation advance online publication, 25 January 2013; doi:10.1038/cdd.2012.169. |
| | |
Authors:
|
S Giovinazzi; V M Morozov; M K Summers; W C Reinhold; A M Ishov |
Related Documents
:
|
12691408 - Microvascular pathological features of immediate perinidal parenchyma in cerebral arter... 15854238 - Carotid tissue levels of argatroban after direct local delivery during carotid endarter... 22405808 - Programmable segmented volumetric modulated arc therapy for respiratory coordination in... 22560808 - Late effects in adult survivors of pediatric cancer: a guide for the primary care physi... 12363178 - Mortality and morbidity in agriculture in the united states. 7738758 - Breast cancer in adolescent females. |
Publication Detail:
|
Type: JOURNAL ARTICLE Date: 2013-1-25 |
Journal Detail:
|
Title: Cell death and differentiation Volume: - ISSN: 1476-5403 ISO Abbreviation: Cell Death Differ. Publication Date: 2013 Jan |
Date Detail:
|
Created Date: 2013-1-25 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 9437445 Medline TA: Cell Death Differ Country: - |
Other Details:
|
Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
|
1] Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL, USA [2] University of Florida Shands Cancer Center, Gainesville, FL, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: IF(1) limits the apoptotic-signalling cascade by preventing mitochondrial remodelling.
Next Document: Two-year results of x-stop interspinous implant for the treatment of lumbar spinal stenosis: a prosp...