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Mechanisms by which calcium regulates the human cardiac voltage-gated sodium channel hH1
(2005-08-12)
The function of the human cardiac voltage-gated sodium channel hH1 is regulated in part by an EF-hand in its C-terminal cytoplasmic domain. The binding of calcium to the EF-hand results in calmodulin-independent, ...
Analysis of ErbB Receptors: Regulation of ErbB-1 Kinase Activation and Localization of ErbB-4 to Membrane Microdomains
(2007-10-03)
The ErbB family of receptor tyrosine kinases regulates cell growth, differentiation, and tumorigenesis. This dissertation contains two independent studies of ErbB-1 and ErbB-4. In one study, the intracellular juxtamembrane ...
Mechanisms of epidermal growth factor receptor tyrosine kinase activation and nuclear trafficking
(2009-09-04)
In several growth factor receptors, the intracellular juxtamembrane (JM) region participates in autoinhibitory interactions that must be disrupted for tyrosine kinase activation. Using alanine scanning mutagenesis, I ...
Quinone Metabolites of Environmental Toxins Poison Topoisomerase IIalpha
(2007-03-31)
Topoisomerases play critical roles in maintaining DNA topology during cellular processes such as DNA replication in eukaryotes. Movement of the replication machinery through the double helix induces positive supercoiling ...
Biochemical and structural analysis of the p58C and p68N domains of DNA polymerase alpha/primase
(2008-07-28)
The replication of DNA occurs through a complex series of steps involving the coordinated action of many proteins. DNA polymerase alpha/primase (pol-prim) is a critical DNA replication factor that synthesizes short RNA-DNA ...
NRIF is an essential component of apoptotic signaling by the p75 neurotrophin receptor
(2005-01-27)
Activation of the p75 neurotrophin receptor leads to a variety of effects within the nervous system, including neuronal apoptosis. Both c-Jun N-terminal kinase (JNK) and the tumor suppressor p53 have been reported to be ...
The DNA Cleavage Reaction of Human Type II Topoisomerases
(2009-02-04)
The work presented in this dissertation examines the DNA cleavage activity of human topoisomerase II. Type II topoisomerases are required for removing DNA knots and tangles and are important chemotherapy drug targets. The ...
Oxidative metabolism of exocyclic DNA adducts
(2008-03-13)
Multiple exocyclic DNA adducts arise from reactions of lipid and DNA peroxidation products with DNA bases. These endogenous lesions are mutagenic; therefore, monitoring adduct levels may provide a means of assessing genomic ...
DNA Lesions as Cellular Poisons of Topoisomerase II-alpha
(2005-11-02)
Topoisomerase II is an essential enzyme that controls DNA topology. This enzyme generates a protein-linked DNA break as a catalytic intermediate. This intermediate, known as the cleavage complex, is present in very low ...
Regulation of Fibronectin Assembly by PLC-gamma1
(2009-04-21)
Phospholipase C-γ1 (PLC-γ1) mediates cell adhesion and migration through an undefined mechanism. Here, we examine the role of PLC-γ1 in cell-matrix adhesion in a hanging drop assay of cell aggregation. Plcg1 Null (-/-) ...