Biochemistry, Biophysics, and Structural Biology Commons^™

Investigating Therapeutic Strategies To Target Metabolic Vulnerabilities Of Nsclc Tumors With Mutant Keap1 Gene, Pranavi Koppula

Dissertations & Theses (Open Access)

The metabolic vulnerability of cancers has long been envisaged as an attractive window to develop novel therapeutic strategies. Metabolic flexibility at the cellular level encompasses the efficient rerouting of anabolic and catabolic pathways in response to varying environmental stimuli to maintain cellular homeostasis and sustain proliferation. The primary objective of this study is to identify metabolic vulnerabilities bestowed by KEAP1/NRF2 signaling axis through SLC7A11. SLC7A11 is a transcriptional target of NRF2, an essential regulator of cellular anti-oxidant response. Under unstressed basal conditions, NRF2 interacts with KEAP1, a tumor suppressor gene and a substrate adaptor protein of the Cullin3-dependent ubiquitin ligase …

Npsd4: A New Player In Sumo-Dependent Dna Repair, Erin Atkinson

Dissertations & Theses (Open Access)

The human genome is under constant threat from sources of damage and stress. Improper resolution of DNA damage lesions can lead to mutations, oncogene activation, and genomic instability. Difficult-to-replicate-loci present barriers to DNA replication that, when not properly resolved, lead to replication fork stalling and collapse and genomic instability.

DNA damage and replication stress trigger signaling cascades potentiated by multiple types of post-translational modifications, including SUMOylation. Through proteomic analysis of proteins involved in SUMOylation following DNA damage, our lab identified an uncharacterized protein that we named New Player in SUMO-dependent DNA damage repair 4 (NPSD4). Through an additional proteomic screen, …

The Functional Analysis Of A Major Tyrosine Phosphorylation Site On Actin, Amelie Simone Cordelia Albrecht

Dissertations & Theses (Open Access)

Actin is an abundant and evolutionarily conserved protein and a key component of the cytoskeleton. Post-translational modifications of actin are emerging as an important mechanism for regulating actin functions, and may form an ‘Actin Code’. In this work, I investigate the role of actin phosphorylation at tyrosine 53 (pY53), one of the most frequently detected actin PTMs, through identifying interaction partners, or ‘readers’, for this modification. Using an SH2 (Src Homology 2) protein domain array, we identify N-terminal SH2 domains of p85, regulatory subunits of Phosphatidylinositol 3-kinase (PI3K), and VAV2, a Rho GTPase guanine nucleotide exchange factor, as phosphorylation-dependent binding …