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Open Access Dissertations

2009

Calorimetry

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Biophysical Analysis Of The Ap1-Dna Interaction, Kenneth L. Seldeen Jun 2009

Biophysical Analysis Of The Ap1-Dna Interaction, Kenneth L. Seldeen

Open Access Dissertations

Jun and Fos are components of the AP1 family of transcription factors that bind to the promoters of a diverse multitude of genes involved in critical cellular responses such as cell growth and proliferation, cell cycle regulation, embryonic development and cancer. The specific protein-DNA interactions are driven by the binding of basic zipper (bZIP) domains of Jun and Fos to TPA response element (TRE) and cAMP response element (CRE) within the promoters of target genes. Here, using a diverse array of biophysical techniques, including in particular isothermal titration calorimetry in conjunction with molecular modeling and semi-empirical analysis, I characterize AP1-DNA …


Physicochemical Studies Of The Grb2-Sos1 Interaction, Caleb B. Mcdonald Jun 2009

Physicochemical Studies Of The Grb2-Sos1 Interaction, Caleb B. Mcdonald

Open Access Dissertations

Grb2, a modular protein comprised of a central SH2 domain flanked between a N-terminal SH3 (nSH3) domain and a C-terminal SH3 (cSH3) domain, is a component of cell signaling networks involved in the transmission of extracellular information in the form of growth factors and cytokines to downstream targets such as transcription factors within the nucleus. The Grb2-Sos1 interaction is mediated through the combinatorial binding of nSH3 and cSH3 domains of Grb2 to various sites - designated S1, S2, S3, and S4 - containing PXpsiPXR motifs within Sos1. Here, using a diverse array of biophysical techniques, including in particular isothermal titration …