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Full-Text Articles in Molecular Biology

Excess No Stabilizes The Luminal Domain Of Stim2 In A Cys-Specific Manner Thereby Regulating Basal Calcium Homeostasis And Store-Operated Calcium Entry, Matthew Novello Sep 2019

Excess No Stabilizes The Luminal Domain Of Stim2 In A Cys-Specific Manner Thereby Regulating Basal Calcium Homeostasis And Store-Operated Calcium Entry, Matthew Novello

Electronic Thesis and Dissertation Repository

Stromal-interaction molecule 2 (STIM2) is an endoplasmic reticulum (ER) membrane-inserted Ca2+-sensing protein which, together with the plasma membrane Ca2+ channel Orai1, regulates basal Ca2+ homeostasis and store-operated Ca2+ entry (SOCE). Recent evidence suggests that S-nitrosylation, which is the covalent attachment of a nitric oxide (NO) moiety to a cysteine thiol, can attenuate the function of the paralog STIM1 protein. Compared to STIM1, STIM2 also functions as a basal Ca2+ homeostatic feedback regulator. Therefore, the objective of my study was to evaluate the susceptibility of STIM2 to S-nitrosylation and the effects that this ...


The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan Feb 2017

The Effects Of Acetylenic Tricyclic Bis-(Cyano Enone) On Cell Migration, Eddie Chan

Electronic Thesis and Dissertation Repository

Although cancer survival rates have significantly improved over the past few decades, the improvements are primarily due to early diagnosis and inhibiting cancer growth. Limited progress has been made in the treatment of cancer metastasis, which contributes to 90% of cancer related deaths, and therapeutic agents targeting the various aspects of metastasis are lacking. One potential approach is to utilize small pharmacological compounds to inhibit tumour cell motility, as a strategy against tumour cell migration, invasion, and metastasis. The acetylenic tricyclic bis-(cyano enone), TBE-31, has been shown to be a promising chemopreventative compound. However, its effects on cell migration ...


Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux Sep 2016

Characterization Of The Catalytic Ck2 Subunits With Substitutions At Residues Involved In Inhibitor Binding, Paul Desormeaux

Electronic Thesis and Dissertation Repository

CK2 is a constitutively active, ubiquitously expressed and pleiotropic serine/threonine protein kinase that is implicated in many cellular functions including tumorigenesis. CK2 has two catalytic subunits, CK2a and CK2a’, that carry out its function in the cell. Previous studies have indicated that inhibitor-refractory mutants have been effective in recovering residual CK2 activity, in the presence of inhibitors, when compared to wild type CK2. Based on these observations, inhibitor-refractory mutants were created for both CK2a and CK2a’ and tested with various concentrations with two CK2-specific inhibitors, CX-4945 and inhibitor VIII. The CK2a triple mutant (V66A/I174A/H160D) was tested in ...


Sirna Targeting Of Thymidylate Synthase, Thymidine Kinase 1 And Thymidine Kinase 2 As An Anticancer Therapy: A Combinatorial Rnai Approach, Christine Di Cresce Apr 2014

Sirna Targeting Of Thymidylate Synthase, Thymidine Kinase 1 And Thymidine Kinase 2 As An Anticancer Therapy: A Combinatorial Rnai Approach, Christine Di Cresce

Electronic Thesis and Dissertation Repository

Thymidylate synthase (TS) is the only de novo source of thymidylate (dTMP) for DNA synthesis and repair. Drugs targeting TS protein are a mainstay in cancer treatment but off-target effects and toxicity limit their use. Cytosolic thymidine kinase (TK1) and mitochondrial thymidine kinase (TK2) contribute to an alternative dTMP-producing pathway, by salvaging thymidine from the tumour milieu, and may modulate resistance to TS-targeting drugs. We have previously shown that TS antisense molecules (oligodeoxynucleotides, ODNs, and small interfering siRNA, siRNA) sensitize tumour cells, both in vitro and in vivo, to TS targeting drugs. As both TS and TKs contribute to cellular ...


Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi Jul 2013

Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi

Electronic Thesis and Dissertation Repository

Clinical studies have demonstrated that intrauterine growth restriction (IUGR) offspring, faced with a nutritional mismatch postpartum, have an increased risk of developing the metabolic syndrome. The maternal protein restriction (MPR) rat model has been extensively studied to investigate the adverse effects of a nutritional mismatch in postnatal life of IUGR offspring. Previous studies have demonstrated that MPR leads to impaired function of the liver, an important metabolic organ. However the underlying mechanisms which predispose these offspring to the metabolic syndrome remain elusive. In the following studies, low protein diet during pregnancy and lactation led to IUGR offspring with decreased liver ...


Human Equilibrative Nucleoside Transporter Subtype 1: Structure-Function Analysis Using Cysteine Mutagenesis And Thiol Modifying Techniques, Jamie Park Aug 2012

Human Equilibrative Nucleoside Transporter Subtype 1: Structure-Function Analysis Using Cysteine Mutagenesis And Thiol Modifying Techniques, Jamie Park

Electronic Thesis and Dissertation Repository

Human equilibrative nucleoside transporter 1 is the main mediator of bi-directional nucleoside flux and is found ubiquitously. Inhibitor and substrate interactions with ENT1 are known to be affected by cysteine-modifying reagents. Our aim was to investigate the importance of cysteine residues in hENT1 function and identify which residues were sensitive to thiol modification for further application of cysteine scanning mutagenesis on extracellular loop 5. Transporter function was assessed by the binding of [3H]NBMPR and the cellular uptake of [3H]2-chloroadenosine. Treatment of hENT1 with the neutral sulfhydryl-modifier methyl methanethiosulfonate (MMTS) enhanced [3H]NBMPR binding but decreased ...


Regulation Of G Protein Signaling By Goloco Motif Containing Proteins, Peishen Zhao Jul 2011

Regulation Of G Protein Signaling By Goloco Motif Containing Proteins, Peishen Zhao

Electronic Thesis and Dissertation Repository

Signal transduction via heterotrimeric G proteins in response to transmembrane G protein-coupled receptors plays a central aspect in how cells integrate extracellular stimuli and produce biological responses. In addition to receptor-mediated activation of heterotrimeric G proteins, during the last few decades, accessory proteins have been found to regulate G protein activity via different mechanisms. Several proteins have been identified that contain multiple G protein regulatory domains. Using various molecular and biochemical approaches, we have characterized the effects of two such proteins, G18 and RGS14, on G protein activity. Both proteins contain a second G protein binding domain in addition to ...