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Full-Text Articles in Molecular Biology

Identifying Functional Components Of The Endoplasmic Reticulum Quality Control And Degradation Factor Edem1, Lydia Lamriben Nov 2018

Identifying Functional Components Of The Endoplasmic Reticulum Quality Control And Degradation Factor Edem1, Lydia Lamriben

Doctoral Dissertations

The ER Degradation-Enhancing Mannosidase-Like protein 1 (EDEM1) is a critical endoplasmic reticulum (ER) quality control factor involved in identifying and directing non-native proteins to the ER-associated protein degradation (ERAD) pathway. However, its recognition and binding properties have remained enigmatic since its discovery. Here we provide evidence for an additional redox-sensitive interaction between EDEM1 and Z/NHK that requires the presence of the single Cys on the α-1 antitrypsin ERAD clients. Moreover, this Cys-dependent interaction is necessary when the proteins are isolated under stringent detergent conditions, ones in which only strong covalent interactions can be sustained. This interaction is inherent to the …


Applications Of Drosophila Melanogaster In Food Science Research, Phoebe Beverly Chen Nov 2018

Applications Of Drosophila Melanogaster In Food Science Research, Phoebe Beverly Chen

Doctoral Dissertations

Drosophila melanogaster is a versatile model organism that provides several unique features, such as highly conserved disease pathways with humans as well as availability of environmental and genetic manipulations. Meanwhile, there is increasing interest in the potential role of bioactive food components, epigallocatechin gallate (EGCG) and conjugated linoleic acid (CLA), in metabolic research. However, there is limited knowledge on the sex-dependent effects of EGCG and CLA on energy metabolism. In this study, Drosophila melanogaster was used to investigate the sex-dependent effects of EGCG and CLA with respect to energy metabolism, including body fat, locomotion, and their key metabolic regulators. We …


The Interplay Between Polarity Regulators, Calcium, And The Actin Cytoskeleton During Tip Growth, Carlisle Bascom Jr Oct 2018

The Interplay Between Polarity Regulators, Calcium, And The Actin Cytoskeleton During Tip Growth, Carlisle Bascom Jr

Doctoral Dissertations

Plant cell growth is a meticulously regulated process whereby the cell wall is selectively loosened to allow for turgor-pressure driven expansion. The rate of expansion must equal delivery of new material, or the cell will lyse. In many plant cells, this process happens diffusely around the cell. However, a number of plant cells have anisotropic shapes that require exquisite spatial control of secretion. One simple example of anisotropic patterning is tip growth; highly polarized cell expansion utilized by pollen tubes, root hairs, and moss protonemata. Investigating the role various molecules have in tip growth sheds light on how plant cells …


Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu Jul 2018

Characterization Of She1 Spindle Role Using Ceullular, Biochemical, And Biophysical Methods, Yili Zhu

Doctoral Dissertations

During development, metaphase spindles undergo large movement and/or rotation to determine the cell division axis. While it has been shown that spindle translocation is achieved by astral microtubules pulling and/or pushing the cortex, how metaphase spindle stability is maintained during translocation remains not fully understood. In budding yeast, our lab has previously proposed a model for spindle orientation wherein the mitotic spindle protein She1 promotes spindle translocation across the bud neck by polarizing cortical dynein pulling activity on the astral microtubules. Intriguingly, She1 exhibits dominant spindle localization throughout the cell cycle. However, whether She1 has any additional role on the …


Extrinsic And Intrinsic Factors In Liver Development, Amrita Palaria Jul 2018

Extrinsic And Intrinsic Factors In Liver Development, Amrita Palaria

Doctoral Dissertations

Liver is the largest internal organ of the human body. It performs a multitude of functions. Therefore, it is provided with a huge regenerative capacity however, because of the same reason it is also prone to various diseases. Hence, it is essential to understand liver development in order to understand liver regeneration and liver diseases to provide better therapeutic targets and solutions. Liver development is orchestrated by a variety of intrinsic and extrinsic factors. The major focus of this dissertation thesis is to elucidate the role of BMP signals and YY1/VEGFA regulated signals in liver development. Liver organogenesis initiates with …


Examining Shsp-Substrate Capture And Chaperone Network Coordination Through Cross-Linking, Keith Ballard Jul 2018

Examining Shsp-Substrate Capture And Chaperone Network Coordination Through Cross-Linking, Keith Ballard

Doctoral Dissertations

Small heat shock proteins (sHSPs) and related α-crystallins are virtually ubiquitous, ATP-independent molecular chaperones linked to protein misfolding diseases. They comprise a conserved core α-crystallin domain (ACD) flanked by an evolutionarily variable N-terminal domain (NTD) and semi-conserved C-terminal extension/domain (CTD). They are capable of binding up to an equal mass of unfolding protein, forming large, heterogeneous sHSP-substrate complexes that coordinate with ATP-dependent chaperones for refolding. To derive common features of sHSP-substrate recognition, I compared the chaperone activity and specific sHSP-substrate interaction sites for three different sHSPs from Arabidopsis (At17.6B), pea (Ps18.1) and wheat (Ta16.9), for which the atomic solution-state structures …


The Molecular Basis Of Caspase-9 Inactivation By Pka And C-Abl Kinases, Banyuhay Paningbatan Serrano Mar 2018

The Molecular Basis Of Caspase-9 Inactivation By Pka And C-Abl Kinases, Banyuhay Paningbatan Serrano

Doctoral Dissertations

Caspases are the cysteine proteases that facilitate the fundamental pathway of programmed cell death or apoptosis. The activation and function of these powerful enzymes are tightly regulated to ensure the faithful execution of apoptosis and prevent untimely cell death. Many deadly human diseases such as cancer, neurodegeneration and autoimmune disorders have been associated with defective activation and faulty regulation of caspases. As such, caspases are considered as attractive drug targets, which when properly controlled, can lead to effective therapeutics for apoptosis-related diseases. Thus, comprehensive investigations of the structure, function and regulation of caspases are necessary to understand the complex mechanisms …


Clpxp Functions In Caulobacter As A Universal And Species-Specific Protease, Robert Vass Mar 2018

Clpxp Functions In Caulobacter As A Universal And Species-Specific Protease, Robert Vass

Doctoral Dissertations

Proteolysis shapes many aspects of cellular survival, including protein quality control and cellular signaling. Powered proteolysis couples ATP hydrolysis with a degradation force that actively probes and interrogates the protein population. ClpXP, exemplifies a conserved two-part protease system charged with powered proteolysis. This protease exists as a regulatory element (ClpX), and a compartmentalized, self-contained peptidase element (ClpP). In Caulobacter crescentus, ClpXP degradation plays a crucial role maintaining proteins that exhibit proper activity, and also triggers the start of cellular differentiation. Substrate elimination requires shared aspects of the protease from both quality control and precision protein destruction functions. Here, the regulatory …


The Role Of The Metallochaperone Hypa In The Acid Survival And Activities Of Nickel Enzymes In Helicobacter Pylori, Heidi Hu Mar 2018

The Role Of The Metallochaperone Hypa In The Acid Survival And Activities Of Nickel Enzymes In Helicobacter Pylori, Heidi Hu

Doctoral Dissertations

Helicobacter pylori is a bacterium that has colonized the human gastric mucosa of over 50% of the world population. Persistent infection can cause gastritis, peptic ulcers, and cancers. The ability of H. pylori to colonize the acidic environment of the human stomach is dependent on the activity of the nickel containing enzymes, urease and NiFe-hydrogenase. The nickel metallochaperone, HypA, was previously shown to be required for the full activity of both enzymes. In addition to a Ni-binding site, HypA also contains a structural Zn site, which has been characterized to alter its averaged structure depending on pH and the presence …


The Heat Shock Cognate 70 Protein (Hsc70) Is A Novel Target For Nobiletin In Colon Cancer Cells, Zili Gao Mar 2018

The Heat Shock Cognate 70 Protein (Hsc70) Is A Novel Target For Nobiletin In Colon Cancer Cells, Zili Gao

Doctoral Dissertations

Nobiletin (NBT) is a unique flavonoid mainly found in citrus fruits, and has been reported to inhibit colon carcinogenesis in multiple rodent models. However, the direct molecular targets of NBT are unknown. Heat shock cognate 70 protein (HSC70) contributes to cancer cell survival and resistance to chemotherapies, thereby the inhibition of HSC70 is a promising strategy in cancer chemoprevention. Using affinity chromatography, proteomics analysis and computer modeling, we demonstrated that NBT bound to HSC70 at its ATP-binding site and specifically inhibited its ATPase activity. The association between HSC70 and HSP90 is critical for the stability of their client proteins, which …