ZFIN ID: ZDB-PUB-130204-4
Depletion of Aurora-A in zebrafish causes growth retardation due to mitotic delay and p53-dependent cell death
Jeon, H.Y., and Lee, H.
Date: 2013
Source: The FEBS journal   280(6): 1518-1530 (Journal)
Registered Authors: Jeon, Hee-Yeon, Lee, Hyunsook
Keywords: Aurora-A, zebrafish, live-imaging, spindle assembly checkpoint (SAC), p53, apoptosis
MeSH Terms:
  • Animals
  • Aurora Kinases
  • Cell Cycle Proteins/genetics
  • Cell Cycle Proteins/metabolism
  • Cell Death
  • Centrosome/enzymology
  • Centrosome/metabolism
  • Centrosome/pathology
  • Cloning, Molecular
  • Disease Models, Animal
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/enzymology
  • Embryo, Nonmammalian/pathology
  • Embryonic Development
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Enzymologic
  • In Situ Nick-End Labeling
  • M Phase Cell Cycle Checkpoints*
  • Microinjections
  • Microscopy, Fluorescence
  • Mitosis
  • Morpholinos/administration & dosage
  • Morpholinos/metabolism
  • Protein-Serine-Threonine Kinases/genetics
  • Protein-Serine-Threonine Kinases/metabolism*
  • Spindle Apparatus/genetics
  • Spindle Apparatus/metabolism*
  • Time Factors
  • Time-Lapse Imaging/methods
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/metabolism*
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 23351126 Full text @ FEBS J.
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ABSTRACT

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.

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