| Depletion of Aurora-A in zebrafish causes growth retardation due to mitotic delay and p53-dependent cell death. | |
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MedLine Citation:
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PMID: 23351126 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aurora-A is a serine/threonine mitotic kinase that is required for centrosome maturation. Many cancer cells overexpress Aurora-A, and several reports have suggested that Aurora-A has prognostic value in the clinical treatment of cancer. Therefore, inhibitors for Aurora-A kinase have been developed. However, studies on Aurora-A are largely done in cancer cell lines and are sometimes controversial. For effective evaluation of Aurora-A inhibitors in cancer treatment, it is essential to understand its function at the organism level. Here, we report the crucial functions of Aurora-A in the homeostasis of spindle organization in mitosis using zebrafish embryogenesis as a model system. Using morpholino technology, we show that the depletion of Aurora-A in zebrafish embryogenesis results in short and bended trunks, accompanied by growth retardation and eventual cell death. Live-imaging and immunofluorescence analyses of the embryos revealed that the developmental defects are due to problems in mitosis, which are manifested through monopolar and disorganized spindle formation. Aurora-A-depleted cells exhibited mitotic arrest with congression failure, leading to the activation of the spindle assembly checkpoint. Cell death in the absence of Aurora-A was partially rescued by co-injection of the p53 morpholino, suggesting that apoptosis after Aurora-A depletion is p53-dependent. The clinical implications of these results relate to the indication that cancers with intact p53 may be the targets for Aurora-A inhibitors. © 2013 The Authors Journal compilation © 2013 FEBS. |
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Authors:
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Hee-Yeon Jeon; Hyunsook Lee |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-28 |
Journal Detail:
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Title: The FEBS journal Volume: - ISSN: 1742-4658 ISO Abbreviation: FEBS J. Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-28 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101229646 Medline TA: FEBS J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2013 The Authors Journal compilation © 2013 FEBS. |
Affiliation:
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Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, 599 Gwanak-Ro, Gwanak-ku, Seoul, 151-742, Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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