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Full-Text Articles in Life Sciences

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu Dec 2020

Mechanisms By Which Mnte-2-Pyp Suppresses Prostate Cancer Cell Growth, Yuxiang Zhu

Theses & Dissertations

Prostate cancer patients are often treated with radiotherapy. MnTE-2-PyP, is a superoxide dismutase (SOD) mimic and a known radioprotector of normal tissues. Our recent work demonstrates that MnTE-2-PyP also inhibits prostate cancer progression with radiotherapy; however, the mechanisms remain unclear. In this thesis, we identified that MnTE-2-PyP-induced intracellular H2O2 levels are critical in inhibiting growth of prostate cancer cells. We found that MnTE-2-PyP induced protein oxidations in PC3 cells and one major group of oxidized protein targets were involved in energy metabolism. The oxidative phosphorylation rates were significantly enhanced in both PC3 and LNCaP cells with MnTE-2-PyP treatment, but mitochondrial …


Elucidating The Role Of Ecdysoneless In Mrna Processing, Irfana Saleem Dec 2020

Elucidating The Role Of Ecdysoneless In Mrna Processing, Irfana Saleem

Theses & Dissertations

The mammalian orthologue of the evolutionarily conserved Ecdysoneless (ECD) protein is required for embryogenesis, cell cycle progression and mitigation of ER stress. However, the molecular mechanisms of ECD function in mammalian cells remain unclear. Here, using mass spectrometry analysis of the mammalian ECD interactome, we identified several components of the mRNA export complexes as binding partners of ECD and then characterized the functional interaction of ECD with key mRNA export-related DEAD BOX protein helicase DDX39A and its associated partners. FISH analysis of Poly-A-tailed mRNAs revealed that ECD depletion/deletion blocks the mRNA export from the nucleus to the cytoplasm. We have …


Deciphering The Catalytic Mechanism Of Human Manganese Superoxide Dismutase, Jahaun Azadmanesh Dec 2020

Deciphering The Catalytic Mechanism Of Human Manganese Superoxide Dismutase, Jahaun Azadmanesh

Theses & Dissertations

The livelihood of human cells is heavily dependent on the ability to modulate the presence of highly reactive oxygen-based molecules termed reactive oxygen species (ROS). In excess, ROS facilitate oxidative damage to the macromolecules of cellular life. SODs are the major family of antioxidant proteins that prevent the buildup of overwhelming amounts of ROS within cells. Sometimes dubbed the “first line of defense” against oxidative damage, SODs defend against the harmful accumulation of ROS by eliminating superoxide. Superoxide is a ROS itself that is also a precursor to much more harmful ROS molecules. MnSOD is the manganese containing form of …


Molecular Insights Into Paf-1 Mediated Pancreatic Homeostasis, Stemness, And Cancer Progression, Saswati Karmakar May 2020

Molecular Insights Into Paf-1 Mediated Pancreatic Homeostasis, Stemness, And Cancer Progression, Saswati Karmakar

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease that has one of the lowest 5-year survival rates among cancers, at just 9%. This grim prognosis is primarily due to the extensive metastatic spread of tumor cells beyond the pancreas at diagnosis and the inability of current therapeutic modalities to treat this aggressive disease effectively. Given that the cancer cells in pancreatic tumors are heterogeneous, the major culprit for cancer initiation, progression, and metastasis remains elusive. Recent studies provide evidence for the existence of highly tumorigenic and drug-resistant cells that are capable of tumor initiation, known as the cancer stem cells …


Novel Regulatory Roles Of Endocytic Membrane Trafficking Proteins In Mitochondrial Homeostasis, Trey Farmer May 2020

Novel Regulatory Roles Of Endocytic Membrane Trafficking Proteins In Mitochondrial Homeostasis, Trey Farmer

Theses & Dissertations

Endocytic membrane trafficking is a basic cell process that is critical for regulating the transport of lipids and proteins. Our lab focuses on the cellular functions and mechanisms of the proteins that regulate these pathways. A key family of regulatory proteins is the C-terminal Eps15 Homology Domain (EHD) protein family. The EHD family includes EHD1-4, which are ubiquitously expressed in mammalian tissues. While these isoforms do have some overlapping functions, each protein also has distinct activities in regulating the shape and fission of membranes throughout the endocytic pathways. Specifically, EHD1 uses ATP hydrolysis to induce constriction and fission of endocytic …