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Title: Dual functions of Caspase-4 in apoptosis and inflammation
Keywords: Caspase-4, inflammation, apoptosis, LPS, ER stress, IL-8
Issue Date: 26-Dec-2007
Citation: UMAYAL LAKSHMANAN (2007-12-26). Dual functions of Caspase-4 in apoptosis and inflammation. ScholarBank@NUS Repository.
Abstract: Caspase-4 regulates endoplasmic reticulum stress-induced apoptosis and mediates TLR4-mediated NF-o +B activation This work investigated the role of caspase-4 in apoptosis and innate immunity. I showed that endoplasmic reticulum (ER) localized caspase-4 is activated only in response to ER stress. Using shRNA-mediated knocked down clones in SHEP1 cells, I showed that caspase-4 is involved in ER mediated apoptosis. Polyglutamine[poly(Q)] aggregates are a characteristic of neurodegenerative disorders. Poly(Q)72 induced apoptosis is reduced in caspase-4 knocked-down clones, thereby arguing a role for caspase-4 in poly(Q) mediated disorders. Toll Like Receptor(TLR) stimulation with different inducers in caspase-4 knocked-down THP1 cells, resulted in a differential transcription and secretion pattern for some cytokines. With TLR4 stimulation, I found that p65 subunit translocation and NF-o +B activation were reduced in the knockdown clones. Hence, I propose a novel role for caspase-4, in TLR4 signaling through NF-o +B activation and cytokine secretion. I also showed that caspase-4 interacts with TRAF6 through its conserved TRAF6 binding site upon LPS stimulation, and forms a complex along with IRAK1 transiently, before NF-o +B activation.
Appears in Collections:Ph.D Theses (Open)

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