Biochemistry, Biophysics, and Structural Biology Commons^™

Regulatory And Functional Aspects Of Foxo3a Transcription Factor And Their Implications In Prostate Cancer, Melissa Elise Dobson

Wayne State University Dissertations

The P13K/Akt pathway is a critical mediator of growth factor signaling involving many cellular functions. The deregulation of this pathway has been shown to be involved in the development of various cancers. One of the main targets of this pathway is FoxO3a, a transcription factor whose target genes are involved in important cellular processes such as apoptosis, cell cycle control, and glucose metabolism. FoxO3a is regulated by various post translational modifications including acetylation, ubiquitination and phosphorylation. The transcription factor is directly phosphorylated by Akt on 3 residues: Threonine 32, Serine 253 and Serine 315. Phosphorylation by Akt generates binding sites …

Unraveling The Molecular Mechanisms Of Insect Diversity, Steven Michael Hrycaj

Wayne State University Dissertations

ABSTRACT

UNRAVELING THE MOLECULAR MECHANISMS OF INSECT DIVERSITY

by

STEVEN MICHAEL HRYCAJ

April 2010

Advisor: Dr. Aleksandar Popadic´

Major: Biological Sciences

Degree: Doctor of Philosophy

While it has long been recognized that the arthropods represent the most diverse animal phylum, the molecular bases defining these large-scale differences in body plans and appendages are only now becoming clear. Specifically, the recent merger between the fields of evolutionary and developmental biology ("evo-devo") have provided several examples illustrating that this extraordinary diversification may be due to evolved variation(s) in the developmental networks that control the formation of these structures. In addition, the delineation …

Isothermal Titration Calorimetry Studies Of Protein-Mediated Interactions And Preliminary Structural Studies Of Tandem Pdz1-2 Domain Of Psd-95 Protein, Ana Jankovic

Wayne State University Dissertations

Protein-mediated interactions that involve multiple ligands in their binding mechanisms are critical for many cellular functions. The primary focus of this dissertation research was to investigate such interactions for two proteins, the PDZ domain and frataxin, involving peptide and metal binding ligands, respectively. The three component projects of this work comprised (1) thermodynamic analysis of PDZ domain binding using calorimetry; (2) X-ray crystallographic structural studies of a PDZ dual domain; and (3) thermodynamic analysis of frataxin binding to iron. The specific goal of the research conducted with the PDZ domains was to understand the mechanism of action of multiple/tandem protein …