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Full-Text Articles in Molecular Biology
Functional Roles For Post-Translational Modifications Of T-Snares In Platelets, Jinchao Zhang
Functional Roles For Post-Translational Modifications Of T-Snares In Platelets, Jinchao Zhang
Theses and Dissertations--Molecular and Cellular Biochemistry
Platelets affect vascular integrity by secreting a host of molecules that promote hemostasis and its sequela. Given its importance, it is critical to understand how platelet exocytosis is controlled. Post-translational modifications, such as phosphorylation and acylation, have been shown to affect signaling pathways and platelet function. In this dissertation, I focus on how these modifications affect the t-SNARE proteins, SNAP-23 and syntaxin-11, which are both required for platelet secretion. SNAP-23 is regulated by phosphorylation. Using a proteoliposome fusion assay, I demonstrate that purified IκB Kinase (IKK) phosphorylated SNAP-23, which increased the initial rates of SNARE-mediated liposome fusion. SNAP-23 mutants …
Integrin Α6Β4 Promotes Pancreatic Cancer Invasion By Altering Dna Repair-Mediated Epigenetics, Brittany L. Carpenter
Integrin Α6Β4 Promotes Pancreatic Cancer Invasion By Altering Dna Repair-Mediated Epigenetics, Brittany L. Carpenter
Theses and Dissertations--Molecular and Cellular Biochemistry
Integrin α6β4 is upregulated in pancreatic carcinoma, where signaling promotes metastatic properties, in part by altering the transcriptome. Such alterations can be accomplished through DNA demethylation of specific promoters, as seen with the pro-metastatic gene S100A4. I found that signaling from integrin α6β4 dramatically upregulates expression of amphiregulin (AREG) and epiregulin (EREG), ligands for the epidermal growth factor receptor (EGFR), and that these ligands promote pancreatic carcinoma invasion. To determine if AREG and EREG are regulated by DNA methylation, pancreatic cancer cells with low AREG and EREG expression were treated with the DNA methyltransferase inhibitor 5-aza-2’-deoxycytidine (5-Aza-CdR), resulting in stable …