Document Detail

Depletion of Aurora-A in zebrafish causes growth retardation due to mitotic delay and p53-dependent cell death.
MedLine Citation:
PMID:  23351126     Owner:  NLM     Status:  Publisher    
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.
Hee-Yeon Jeon; Hyunsook Lee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-28
Journal Detail:
Title:  The FEBS journal     Volume:  -     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 The Authors Journal compilation © 2013 FEBS.
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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