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

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)62-72
Number of pages11
JournalJournal of Neuroscience Research
Volume81
Issue number1
DOIs
Publication statusPublished - 2005 Jul 1

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Regulation of the proapoptotic activity of Huntingtin interacting protein 1 by Dyrk1 and caspase-3 in hippocampal neuroprogenitor cells'. Together they form a unique fingerprint.

  • Cite this