Drosophila melanogasterGlutamate-Cysteine Ligase Activity Is Regulated by a Modifier Subunit with a Mechanism of Action Similar to That of the Mammalian Form

Fraser, Jennifer A.; Saunders, Robert D. C.; McLellan, Lesley I.

doi:10.1074/jbc.m106683200

Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer (2020)
Journal Article
Meehan, J., Gray, M., Martínez-Pérez, C., Kay, C., Pang, L. Y., Fraser, J. A., …Turnbull, A. K. (2020). Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer. Frontiers in Oncology, 10, https://doi.org/10.3389/fonc.20

Radiotherapy remains an important treatment modality in nearly two thirds of all cancers, including the primary curative or palliative treatment of breast cancer. Unfortunately, largely due to tumor heterogeneity, tumor radiotherapy response rates ca... Read More about Precision Medicine and the Role of Biomarkers of Radiotherapy Response in Breast Cancer.

hASH1 nuclear localization persists in neuroendocrine transdifferentiated prostate cancer cells, even upon reintroduction of androgen (2019)
Journal Article
Fraser, J. A., Sutton, J. E., Tazayoni, S., Bruce, I., & Poole, A. V. (2019). hASH1 nuclear localization persists in neuroendocrine transdifferentiated prostate cancer cells, even upon reintroduction of androgen. Scientific Reports, 9, Article 19076 (2019

Neuroendocrine prostate cancer (NEPC) is thought to arise as prostate adenocarcinoma cells transdifferentiate into neuroendocrine (NE) cells to escape potent anti-androgen therapies however, the exact molecular events accompanying NE transdifferentia... Read More about hASH1 nuclear localization persists in neuroendocrine transdifferentiated prostate cancer cells, even upon reintroduction of androgen.

Silver nanoparticles promote the emergence of heterogeneic human neutrophil sub-populations (2018)
Journal Article
Kemp, S., Young, L., Ross, M., Prach, M., Hutchison, G. R., Malone, E., & Fraser, J. A. (2018). Silver nanoparticles promote the emergence of heterogeneic human neutrophil sub-populations. Scientific Reports, 8(1), Article 7506. https://doi.org/10.1038/s4

Neutrophil surveillance is central to nanoparticle clearance. Silver nanoparticles (AgNP) have numerous uses, however conflicting evidence exists as to their impact on neutrophils and whether they trigger damaging inflammation. Neutrophil’s importanc... Read More about Silver nanoparticles promote the emergence of heterogeneic human neutrophil sub-populations.

Preferential activation of HIF-2α adaptive signalling in neuronal-like cells in response to acute hypoxia (2017)
Journal Article
Martín-Aragón Baudel, M. A. S., Rae, M. T., Darlison, M. G., Poole, A. V., & Fraser, J. A. (2017). Preferential activation of HIF-2α adaptive signalling in neuronal-like cells in response to acute hypoxia. PLOS ONE, 12(10), Article e0185664. https://do

Stroke causes severe neuronal damage as disrupted cerebral blood flow starves neurons of oxygen and glucose. The hypoxia inducible factors (HIF-1α and HIF-2α) orchestrate oxygen homeostasis and regulate specific aspects of hypoxic adaptation. Here we... Read More about Preferential activation of HIF-2α adaptive signalling in neuronal-like cells in response to acute hypoxia.

Phosphomimetic Mutation of the N-Terminal Lid of MDM2 Enhances the Polyubiquitination of p53 through Stimulation of E2-Ubiquitin Thioester Hydrolysis (2014)
Journal Article
Fraser, J. A., Worrall, E. G., Lin, Y., Landre, V., Pettersson, S., Blackburn, E., Walkinshaw, M., Muller, P., Vojtesek, B., Ball, K., & Hupp, T. R. (2015). Phosphomimetic Mutation of the N-Terminal Lid of MDM2 Enhances the Polyubiquitination of p53 throu

Mouse double minute 2 (MDM2) has a phosphorylation site within a lid motif at Ser17 whose phosphomimetic mutation to Asp17 stimulates MDM2-mediated polyubiquitination of p53. MDM2 lid deletion, but not Asp17 mutation, induced a blue shift in the λm... Read More about Phosphomimetic Mutation of the N-Terminal Lid of MDM2 Enhances the Polyubiquitination of p53 through Stimulation of E2-Ubiquitin Thioester Hydrolysis.

Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development (2014)
Journal Article
Girardi, G., Fraser, J., Lennen, R., Vontell, R., Jansen, M., & Hutchison, G. (2015). Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict

In the current study, we have developed a magnetic resonance imaging-based method for non-invasive detection of complement activation in placenta and foetal brain in vivo in utero. Using this method, we found that anti-complement C3-targeted ultras... Read More about Imaging of activated complement using ultrasmall superparamagnetic iron oxide particles (USPIO) - conjugated vectors: an in vivo in utero non-invasive method to predict placental insufficiency and abnormal fetal brain development.

A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: II. A MODEL IN WHICH PHOSPHORYLATION AT SER269 INDUCES A MUTANT CONFORMATION TO p53. (2010)
Journal Article
Fraser, J. A., Madhumalar, A., Blackburn, E., Bramham, J., Walkinshaw, M. D., Verma, C., & Hupp, T. R. (2010). A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: II. A MODEL IN WHICH PHOSPHORYLATION AT SER269 INDUCES A MUTANT CONFORMATION TO p53. Journal of Biological Chemistry, 285, 37773-37786. https://doi.org/10.1074/jbc.M110.143107

The p53 DNA-binding domain harbors a conformationally flexible multiprotein binding site that regulates p53 ubiquitination. A novel phosphorylation site exists within this region at Ser269, whose phosphomimetic mutation inactivates p53. The phosphomi... Read More about A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: II. A MODEL IN WHICH PHOSPHORYLATION AT SER269 INDUCES A MUTANT CONFORMATION TO p53..

A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: I. PHOSPHORYLATION AT SER269 IN VIVO IS LINKED TO INACTIVATION OF p53 FUNCTION. (2010)
Journal Article
Fraser, J. A., Vojtesek, B., & Hupp, T. R. (2010). A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: I. PHOSPHORYLATION AT SER269 IN VIVO IS LINKED TO INACTIVATION OF p53 FUNCTION. Journal of Biological Chemistry, 285, 37762-37772. https://doi.org/10.1074/jbc.M110.143099

p53 is a thermodynamically unstable protein containing a conformationally flexible multiprotein docking site within the DNA-binding domain. A combinatorial peptide chip used to identify the novel kinase consensus site RXSΦ(K/D) led to the discovery o... Read More about A Novel p53 Phosphorylation Site within the MDM2 Ubiquitination Signal: I. PHOSPHORYLATION AT SER269 IN VIVO IS LINKED TO INACTIVATION OF p53 FUNCTION..

A Central Role for CK1 in Catalyzing Phosphorylation of the p53 Transactivation Domain at Serine 20 after HHV-6B Viral Infection (2008)
Journal Article
MacLaine, N. J., Øster, B., Bundgaard, B., Fraser, J. A., Buckner, C., Lazo, P. A., …Hupp, T. R. (2008). A Central Role for CK1 in Catalyzing Phosphorylation of the p53 Transactivation Domain at Serine 20 after HHV-6B Viral Infection. Journal of Biological Chemistry, 283, 28563-28573. https://doi.org/10.1074/jbc.M804433200

The tumor suppressor protein p53 is activated by distinct cellular stresses including radiation, hypoxia, type I interferon, and DNA/RNA virus infection. The transactivation domain of p53 contains a phosphorylation site at Ser20 whose modification st... Read More about A Central Role for CK1 in Catalyzing Phosphorylation of the p53 Transactivation Domain at Serine 20 after HHV-6B Viral Infection.

The MDM2 Ubiquitination Signal in the DNA-Binding Domain of p53 Forms a Docking Site for Calcium Calmodulin Kinase Superfamily Members (2007)
Journal Article
Craig, A. L., Chrystal, J. A., Fraser, J. A., Sphyris, N., Lin, Y., Harrison, B. J., …Hupp, T. R. (2007). The MDM2 Ubiquitination Signal in the DNA-Binding Domain of p53 Forms a Docking Site for Calcium Calmodulin Kinase Superfamily Members. Molecular a

Genetic and biochemical studies have shown that Ser20 phosphorylation in the transactivation domain of p53 mediates p300-catalyzed DNA-dependent p53 acetylation and B-cell tumor suppression. However, the protein kinases that mediate this modification... Read More about The MDM2 Ubiquitination Signal in the DNA-Binding Domain of p53 Forms a Docking Site for Calcium Calmodulin Kinase Superfamily Members.

Chemical Genetics Approach to Identify Peptide Ligands that Selectively Stimulate DAPK-1 Kinase Activity (2007)
Journal Article
Fraser, J. A., & Hupp, T. R. (2007). Chemical Genetics Approach to Identify Peptide Ligands that Selectively Stimulate DAPK-1 Kinase Activity. Biochemistry, 46(10), 2655-2673. https://doi.org/10.1021/bi061562j

Dissection of signal transduction pathways has been advanced by classic genetic approaches including targeted gene deletion and siRNA-based inhibition of gene product synthesis. Chemical genetics is a biochemical approach to develop small peptide-mim... Read More about Chemical Genetics Approach to Identify Peptide Ligands that Selectively Stimulate DAPK-1 Kinase Activity.

Antioxidant and cytoprotective responses to redox stress (2004)
Journal Article
Mathers, J., Fraser, J. A., McMahon, M., Saunders, R. D. C., Hayes, J. D., & McLellan, L. I. (2004). Antioxidant and cytoprotective responses to redox stress. Biochemical Society symposia, 71, 157-176. https://doi.org/10.1042/bss0710157

Aerobic cells produce reactive oxygen species as a consequence of normal cellular metabolism, and an array of antioxidant systems are in place to maintain the redox balance. When the redox equilibrium of the cell is upset by pro-oxidant environmental... Read More about Antioxidant and cytoprotective responses to redox stress.

The Modifier Subunit of Drosophila Glutamate-Cysteine Ligase Regulates Catalytic Activity by Covalent and Noncovalent Interactions and Influences Glutathione Homeostasis in Vivo (2003)
Journal Article
Fraser, J. A., Kansagra, P., Kotecki, C., Saunders, R. D. C., & McLellan, L. I. (2003). The Modifier Subunit of Drosophila Glutamate-Cysteine Ligase Regulates Catalytic Activity by Covalent and Noncovalent Interactions and Influences Glutathione Homeostas

Glutamate-cysteine ligase (GCL) has a key influence on glutathione homeostasis. It has been proposed that mammalian GCL is regulated by the redox environment, and we show here that cysteine residues in the Drosophila melanogaster GCL modifier subunit... Read More about The Modifier Subunit of Drosophila Glutamate-Cysteine Ligase Regulates Catalytic Activity by Covalent and Noncovalent Interactions and Influences Glutathione Homeostasis in Vivo.

Drosophila melanogasterGlutamate-Cysteine Ligase Activity Is Regulated by a Modifier Subunit with a Mechanism of Action Similar to That of the Mammalian Form (2001)
Journal Article
Fraser, J. A., Saunders, R. D. C., & McLellan, L. I. (2002). Drosophila melanogasterGlutamate-Cysteine Ligase Activity Is Regulated by a Modifier Subunit with a Mechanism of Action Similar to That of the Mammalian Form. Journal of Biological Chemistry, 27

Glutamate-cysteine ligase (GCL) plays an important role in regulating glutathione homeostasis. In mammals, it comprises a catalytic (GCLC) and modifier (GCLM) subunit. The existence of a modifier subunit in invertebrates has not been described to dat... Read More about Drosophila melanogasterGlutamate-Cysteine Ligase Activity Is Regulated by a Modifier Subunit with a Mechanism of Action Similar to That of the Mammalian Form.

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