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Full-Text Articles in Physical Sciences and Mathematics
The Regulation Of Atg9a-Mediated Aggrephagy By An Ulk1-Independent Atg13-Atg101 Complex, Joshua Youngs
The Regulation Of Atg9a-Mediated Aggrephagy By An Ulk1-Independent Atg13-Atg101 Complex, Joshua Youngs
Undergraduate Honors Theses
Aggrephagy, a type of autophagy, is an essential cellular process by which protein aggregates are collected and broken down in the lysosome. Protein aggregates are implicated in several diseases including Alzheimer’s disease, diabetes, and cancer. Here, we investigate the ATG13-ATG101 protein complex, a sub-complex of the canonical ULK1 complex whose regulatory role in aggrephagy is not completely understood. We also develop a protein fragment complementation (PFC) assay using the biotin ligase TurboID to study the functions of the ATG13-ATG101 complex with increased specificity. We demonstrate that ATG13 is required for optimal degradation of p62-ubiquitin condensates. We also show that a …
Improvement In 14-3-3 Binding Site Prediction, Katherine K. Mccormack
Improvement In 14-3-3 Binding Site Prediction, Katherine K. Mccormack
ScholarsArchive Data
The 14-3-3 family of phospho-binding proteins regulate a variety of major cellular processes through interaction with a network of dynamic proteins. Deregulation of the 14-3-3 interaction network contributes to a variety of degenerative disorders and cancers. Our lab focuses on identifying novel 14-3-3 interactions and understanding how 14-3-3 binding regulates protein function. A major gap in this process is that identifying the phospho-site where 14-3-3 docks on a given protein is time- and resource-consuming. Prediction algorithms have been developed to predict canonical 14-3-3 binding sites, however, there are many non-canonical sites that existing software is unable to predict. To fill …
Functional And Mechanistic Insight Into The Role Of Atg9a In Autophagy, Vajira Kaushalya Weerasekara
Functional And Mechanistic Insight Into The Role Of Atg9a In Autophagy, Vajira Kaushalya Weerasekara
Theses and Dissertations
The bulk degradative process of macroautophagy requires the dynamic growth of autophagosomes, which carry cellular contents to the lysosome for recycling. Atg9A, a multi-pass transmembrane protein, is an apical regulator of autophagosome growth, yet its regulatory mechanism remains unclear. Our work suggests that hypoxia (low glucose and oxygen) triggers a rearrangement of the small adapter protein 14-3-3ζ interactome. Our data suggest that the localization of mammalian Atg9A to autophagosomes requires phosphorylation on the C terminus of Atg9A at S761, which creates a 14-3-3z docking site. Under basal conditions, this phosphorylation is maintained at a low level and is dependent on …
Autophagy-Mediated Mechanisms Of Chemoresistance In Cancer, David Broadbent, Dr. Joshua Andersen
Autophagy-Mediated Mechanisms Of Chemoresistance In Cancer, David Broadbent, Dr. Joshua Andersen
Journal of Undergraduate Research
The resistance of tumor cells to chemotherapy is a critical problem in the clinic and is a common cause of mortality in cancer. Emerging data suggests that resistance to chemotherapy is caused by a tumor-expressed protein called 14-3-3ζ, yet the mechanism to explain 14-3-3ζ-mediated chemoresistance is not completely understood (1). Rapid growing tumors often outgrow their blood supply resulting in regions of hypoxia (low glucose and oxygen). These cells must adapt or die and those that do adapt often become metastatic and chemoresistant. A recently proposed mechanism by which cancer cells are able to adapt to hypoxia is via autophagy, …
Pyridinium Bis-Retinoids A2-Dopamine And A2-Cadaverine: Implications In Age-Related Macular Degeneration And Cancer, Mckenzie Ruth Pew
Pyridinium Bis-Retinoids A2-Dopamine And A2-Cadaverine: Implications In Age-Related Macular Degeneration And Cancer, Mckenzie Ruth Pew
Theses and Dissertations
Age-related macular degeneration (AMD) is the leading cause of blindness in the United States of America. The pyridinium bis-retinoid A2-ethanolamine (A2E) has been implicated to play a role in AMD. We have observed novel pyridinium bis-retinoids through melanolipofuscin and human RPE extractions that may also play a role in the pathology of AMD. We have begun the construction of an amino-retinoid library in order to identify these ocular compounds. The compounds from the amino-retinoid library are also used in a targeted and triggered drug delivery system for treating cancer. Folic acid is coupled with the amino-retinoids to specifically target cancer …