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Mechanistics Of Prothymosin Alpha And Nrf2 In The Keap1-Nrf2 Mediated Oxidative Stress Response, Halema Khan
Mechanistics Of Prothymosin Alpha And Nrf2 In The Keap1-Nrf2 Mediated Oxidative Stress Response, Halema Khan
Electronic Thesis and Dissertation Repository
In an effort to dissect the mechanism of interaction of IDPs, in this thesis we focus on Prothymosin a (ProTa) and nuclear factor erythroid 2-related factor 2 (Nrf2), intrinsically disordered proteins, in the Nrf2 mediated oxidative stress response. Kelch-like ECH-associated protein 1 (Keap1) is an inhibitor of Nrf2, a key transcription factor of cytoprotective genes. Under unstressed conditions, Keap1 interacts with Nrf2 in the cytoplasm via its Kelch domain and suppresses Nrf2 activity. During oxidative stress, Nrf2 is released from Keap1 and is shuttled to the nucleus, where it initiates pro cell survival gene transcription. ProTa also interacts with the …
Characterization Of The Interaction Between The Parkin Ubiquitin-Like Domain And Ataxin-3 Ubiquitin Interacting Domains, Jane J. Bai
Electronic Thesis and Dissertation Repository
The ubiquitin signaling pathway (USP) consists of hundreds of enzymes which are tightly regulated for proper maintenance of intracellular protein level homeostasis. The main goals of this thesis were to characterize the interaction of two proteins involved in the USP, the E3 ubiquitin ligase called parkin, and the Deubiquitinating (DUB) enzyme, ataxin-3. The effect of disease-state substitutions in the parkin ubiquitin-like domain (UbLD) on the interaction with ataxin-3 was investigated through NMR 1H-15N HSQC titration experiments and affinity binding assays. The three UIM regions in ataxin-3bind the hydrophobic patch of parkin UbLD (KD = 680 μM) …