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Novel Role Of Endoplasmic Reticulum-Associated Degradation In The Regulation Of Ceruloplasmin, Stephen William Hippleheuser
Novel Role Of Endoplasmic Reticulum-Associated Degradation In The Regulation Of Ceruloplasmin, Stephen William Hippleheuser
Wayne State University Theses
Ceruloplasmin (Cp) is a secreted ferroxidase produced by the hepatocytes that assists in the transport of iron throughout the human body. In human aceruloplasminemia patients, due to Cp deficiency excess intracellular iron buildup leads to ailments like liver cirrhosis, neurodegeneration, and blindness. We recently found that the biogenesis of Cp in the endoplasmic reticulum (ER) is regulated by a principal ER quality-control process, ER-associated degradation (ERAD). ERAD clears misfolded ER proteins for cytosolic proteasomal degradation, with the Sel-1 suppressor of lin-12-like (Sel1L)-HMG-CoA reductase degradation 1 (Hrd1) protein complex representing the most conserved branch in mammals. Interestingly, we found that Sel1L-Hrd1 …
The Role Of Ceruloplasmin In Colitis, Bakytzhan Bakhautdin
The Role Of Ceruloplasmin In Colitis, Bakytzhan Bakhautdin
ETD Archive
Ceruloplasmin (Cp) is an acute phase, plasma protein with multiple enzymatic activities consistent with both pro- and anti-inflammatory functions. Our laboratory has recently reported the presence of Cp in intestinal epithelial cells. To determine the potential role of Cp in intestinal inflammation, we induced colitis in Cp-deficient mice by continuous administration of dextran sodium sulfate (DSS) ad libitum in the drinking water. The Cp-null mice rapidly lost weight and all were moribund by day 14, while about 90 of the wild-type (WT) mice survived at least 20 days. Higher amounts of TNF-alpha, and neutrophil (KC) and macrophage (MCP-1) chemokines, were …
An Insight Into Gait Complex Mediated Translational Silencing, Purvi Kapasi
An Insight Into Gait Complex Mediated Translational Silencing, Purvi Kapasi
ETD Archive
Transcript-specific translational control restricts macrophage inflammatory gene expression. The pero-inflammatory cytokine IFN-Îđ induces the phosphorylation of human ribosomal protein L13a and its subsequent release from 60S ribosome. L13a is a component of the interferon-gamma-activated inhibitor of translation (GAIT). The GAIT complex binds a defined element in the 3'-untranslated region (UTR) of ceruloplasmin (Cp) mRNA and causes delayed silencing of translation. In this research, we elucidate the molecular mechanism underlying L13a translational silencing activity. L13a mediates translational silencing particularly, when driven by internal ribosome entry sites (IRESs) that requires the initiation factor eIF4G, but is resistant to silencing when driven by …