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|Title: ||Roles of RING domain proteins, Ring1B and Ring13, in apoptosis|
|Authors: ||Wong, Chung Kai|
|Issue Date: ||2007 |
|Abstract: ||Both Caspase-3 and Caspase-9 play critical roles in the execution of mitochondria-mediated apoptosis. Caspase-9 binds to Apaf-1 in the presence of cytochrome c and dATP/ATP, and is activated by self-cleavage. Caspase-3 is activated by cleavage of caspase-8 and caspase-9. Over hundred direct caspase-3 substrates are identified whereas only few direct caspase-9 substrates are known. Here, we demonstrate that Ring1B, a component of polycomb protein complex that plays an important role in modulating chromatin structures, is a direct substrate of active caspase-3 and caspase-9 both in vitro and in vivo. The specific cleavage sites for caspase-3 and caspase-9 were mapped to Asp175 and Asp208, respectively. Importantly, cleavage of Ring1B by active caspases-3 and caspase-9 triggers the redistribution of Ring1B, from exclusive nuclear localization to even distribution throughout the entire cell. The transcriptional repression activity of Ring1B was also disrupted by caspase cleavage. Our data suggest that caspases-3 and caspase-9 play novel roles in transcription by regulating polycomb protein function through direct cleaving of Ring1B.
To further explore roles of Ring protein in apoptosis we initiated functional screening using retroviral system and identified a novel gene, Ring13, as one of the potential candidates that confer resistance to UV-induced apoptosis. Interestingly, over-expression of Ring13 can induce Caspase-3 dependent apoptosis. Furthermore, we demonstrated that Ring13 was localized to ER and mediated ER stress and JNK activation. Our data suggest that Ring13 is important in mediating UV and ER stress-induced apoptosis.|
|Description: ||Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2007|
xv, 122 leaves : ill. (some col.) ; 30 cm
HKUST Call Number: Thesis BIOL 2007 Wong
|Appears in Collections:||BIOL Doctoral Theses|
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