Title page for etd-0629113-235902


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URN etd-0629113-235902
Author Ding-Yan Hsiao
Author's Email Address No Public.
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Department Biological Sciences
Year 2012
Semester 2
Degree Master
Type of Document
Language English
Title Mutagenesis of BH3-like domain of Bcl2L12 identifies residues critical for apoptosis in GBM cell lines
Date of Defense 2013-07-25
Page Count 44
Keyword
  • Bcl2 family proteins
  • GBM
  • Bcl2L12
  • BH3-like domain
  • apoptosis
  • Abstract Previous reports have suggested that Bcl2L12 is overexpressed in glioblastoma (GBM) and directly contributies anti-apoptotic effect by inhibiting caspase-3/7 and p53, a mechanism of inhibition of post-mitochondria apoptosis induction. Bcl2L12 is known as a member of Bcl2 family, (generally, Bcl2 family members imply their anti-/pro-apoptotic function by interacting with others Bcl2 family members). This study identify whether Bcl2L12 also confers an anti-apoptotic role by interacting with others Bcl2 family members. First, used yeast two-hybrid assay to identify Bcl2L12 has the ability to interact with BclxL and Bcl2. To explore the region responsible for interaction with Bcl2 family members on Bcl2L12, Bcl2L12 fragments have been analyzed by using yeast two-hybrid assay and combined ISIS program to predict the interacting region for BclxL at Bcl2L12212-216. Thereafter, aligned Bcl2L12 with Bcl2 family members, compared interacting pattern of Bax BH3 domain and 3D structure models with Bcl2 members. Five site-directed mutants corresponding to hydrophobic and charge residues within this region were generated to examine whether these residues are critical for Bcl2L12 or Bax-mediated binding. Our data did show the h2 residue (L213) is essential for the Bcl2L12 and Bax interaction with BclxL. Altogether, the data revealed that a novel BH3-like domain on Bcl2L12 may be responsible for its interaction as similar as BH3 domain in Bax. Moreover, ectopic overexpressed Bcl2L12wt and BH3-like domain mutant in GBM cell lines resulted in variations on expression levels of apoptotic markers. We concluded that BH3-like domain does exist and is also critical for Bcl2L12’s anti-apoptotic role.
    Advisory Committee
  • Chi-Huei Wang - chair
  • Ming-Hong Tai - co-chair
  • Ching-Mei Hsu - co-chair
  • Yi-Ren Hong - advisor
  • Files
  • etd-0629113-235902.pdf
  • Indicate in-campus at 5 year and off-campus access at 5 year.
    Date of Submission 2013-07-30

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