Shin Ae Choi

Publications (2)6.28 Total impact

• Article: Huntingtin-interacting protein 1-mediated neuronal cell death occurs through intrinsic apoptotic pathways and mitochondrial alterations.

  Shin Ae Choi, Steven J Kim, Kwang Chul Chung
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  ABSTRACT: Huntingtin interacting protein-1 (Hip1) is known to be associated with the N-terminal domain of huntingtin. Although Hip1 can induce apoptosis, the exact upstream signal transduction pathways have not been clarified yet. In the present study, we examined whether activation of intrinsic and/or extrinsic apoptotic pathways occurs during Hip1-mediated neuronal cell death. Overexpression of Hip1 induced cell death through caspase-3 activation in immortalized hippocampal neuroprogenitor cells. Interestingly, proteolytic processing of Hip1 into partial fragments was observed in response to Hip1 transfection and apoptosis-inducing drugs. Moreover, Hip1 was found to directly bind to and activate caspase-9. This promoted cytosolic release of cytochrome c and apoptosis-inducing factor via mitochondrial membrane perturbation. Furthermore, Hip1 could directly bind to Apaf-1, suggesting that the neurotoxic signals of Hip1 transmit through the intrinsic mitochondrial apoptotic pathways and the formation of apoptosome complex.
  FEBS Letters 11/2006; 580(22):5275-82. · 3.54 Impact Factor
• Article: Regulation of the proapoptotic activity of huntingtin interacting protein 1 by Dyrk1 and caspase-3 in hippocampal neuroprogenitor cells.

  Jae Eun Kang, Shin Ae Choi, Jung Bum Park, Kwang Chul Chung
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  ABSTRACT: Dual specific protein kinase Dyrks are thought to play a key role in the regulation of cell growth in a variety of cellular systems. Interestingly, human Dyrk1 is mapped to the Down's syndrome (DS) critical region on chromosome 21, and thought to be a candidate gene responsible for the mental retardation of DS patients. Huntingtin-interacting protein 1 (Hip-1), a proapoptotic mediator, is implicated as a molecular accomplice in the pathogenesis of Huntington's disease. In the present study we found that Dyrk1 selectively binds to and phosphorylates Hip-1 during the neuronal differentiation of embryonic hippocampal neuroprogenitor (H19-7) cells. The Dyrk1-mediated phosphorylation of Hip-1, in response to bFGF, resulted in the blockade of Hip-1-mediated neuronal cell death as well as the enhancement of neurite outgrowth. Furthermore, the addition of etoposide to proliferating H19-7 cells caused the diminished binding of Hip-1 to Dyrk1 and the levels of phosphorylated Hip-1 remarkably decreased. Simultaneously, the dissociated Hip-1 from Dyrk1 bound to caspase-3 in response to etoposide, which led to its activation and consequently cell death in H19-7 cells. These data suggest that the phosphorylation of Hip-1 by Dyrk1 has a dual role in regulating neuronal differentiation and cell death. The interaction between Dyrk1 and Hip-1 appeared to be differentially modulated by different kinds of stimuli, such as bFGF and etoposide in H19-7 cells.
  Journal of Neuroscience Research 08/2005; 81(1):62-72. · 2.74 Impact Factor