Title page for etd-0608115-114035


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URN etd-0608115-114035
Author Chia-hua Chou
Author's Email Address No Public.
Statistics This thesis had been viewed 5354 times. Download 346 times.
Department Biological Sciences
Year 2014
Semester 2
Degree Ph.D.
Type of Document
Language English
Title Characterize the molecular mechanisms of mitochondrial GSK3beta-Drp1 and centrosomal Ninein-AIBp-Aurora A/ Plk1 protein-protein interactions
Date of Defense 2015-06-24
Page Count 151
Keyword
  • hNinein
  • GSK3beta
  • mitochondria
  • AIBp
  • Drp1
  • centrosome
  • Aurora A
  • Plk1
  • Abstract Glycogen synthase kinase-3beta (GSK3beta) has been reported to participate in several signaling pathways and crucial for cell development, metabolic homeostasis, neuronal growth and differentiation, cell polarity, cell fate and apoptosis. In the past several years, we pay great efforts to study protein-protein interactions by yeast two-hybrid techniques, and identified many novel GSK3beta interaction proteins including dynamin-like protein (Drp1), hNinein, CGI-99, CABYR variant, GSKIP and Astrin. Recently, we also used two-hybrid platform to discover a novel Aurora A and hNinein binding protein, AIBp. At first part of this study, we continued our research on Drp1. Drp1 is a mitochondria fission protein, involved in neurodegenerative diseases in terms of affecting mitochondrial dynamics. We clearly demonstrated that GSK3beta-mediated phosphorylation at Ser693 of Drp1 and the region of Drp1634-690 and Lys679 are crucial for GSK3beta interaction. We also revealed that mitochondrial elongation due to ectopic expression of Drp1 S693D mutants may be associated with enhanced resistance to H2O2-induced mitochondrial fragmentation and ensuing apoptosis via down-regulating cytochrome c release, capase-3, -7 and PARP activation, rather than inducing autophagy. At the second part of the study, we demonstrated that AIBp also interacts with Plk1, which subsequently promotes Aurora-A–mediated Plk1 activation. In contrast, it blocks the hNinein phosphorylation mediated by Aurora A and Plk1. Knockdown of AIBp expression caused down-regulation of Aurora A Thr288, Plk1 Thr210 phosphorylation and mislocalization of ch-TOG to centrosomes, resulted in phenotypes of multiple spindle pole formation and chromosome misalignment. We suggested that the interplay of hNinein, AIBp, Aurora-A, and Plk1 may contributes to mitotic entry and bipolar spindle assembly during mitotic progression.
    Advisory Committee
  • Jiin-Tsuey Cheng - chair
  • Pei-Jung Lu - co-chair
  • Hsiao, Michael Hong-Shen - co-chair
  • Chi-Ying F. Huang - co-chair
  • Yi-Ren Hong - advisor
  • Ching-Mei Hsu - advisor
  • Files
  • etd-0608115-114035.pdf
  • Indicate in-campus at 0 year and off-campus access at 1 year.
    Date of Submission 2015-07-08

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