FEBS Journal Award Session

Seoul National University, KR

Depletion of Aurora-A in zebrafish causes growth retardation due to mitotic delay and p53-dependent cell death

Aurora-A is a serine/threonine mitotic kinase that is required for centrosome maturation. Many cancer cells over-express 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 performed 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 homeostasis of spindle organization in mitosis using zebrafish embryogenesis as a model system. Using morpholino technology, we show that depletion of Aurora-A in zebrafish embryogenesis results in short bent 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, manifested through monopolar and disorganized spindle formation. Aurora-A-depleted cells exhibited mitotic arrest with congression failure, leading to 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 Aurora-A inhibitors may be effective towards cancers with intact p53.

Biography

Hee-Yeon Jeon was born in Incheon, South Korea. As a little girl, she was very talented in music, spending most of her childhood as a member of choir and playing Gayaguem. This early interest in music made her an active and confident individual. She was educated at Kyunggi girls’ high school, which is one of the most time-honored schools in Korea and it was where she grew her zeal for science. When she got her B.S degree in Life Sciences at Ewha Womans University, Korea, she graduated cum laude and a year earlier than others for her achievement. As a Ph.D. student at Seoul National University under the supervision of Professor Hyunsook Lee, she was selected for the Seoul Fellowship in biology. She studied on the role of mitotic kinase Aurora-A in the zebrafish system and reported the results in FEBS Journal, 2013. She has recently embarked on a project to generate CRISPR/Cas9 knockout zebrafish targeting important mitotic players such as Aurora-B, Plk1, and BubR1. Now she is studying on “How chromosome missegregation in BubR1 acetylation-deficient mice leads to genome-wide alteration” especially in the view of “lymphomagenesis” using transcriptome analysis and mouse genetics.