A5089766093- Prostate Cancer Treatment and Research
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Genomics and Chromatin Dynamics
- Plant biochemistry and biosynthesis
- Cancer-related Molecular Pathways
- Estrogen and related hormone effects
- Enzyme Structure and Function
- NF-κB Signaling Pathways
- Protein Kinase Regulation and GTPase Signaling
- Steroid Chemistry and Biochemistry
- Microtubule and mitosis dynamics
- Caveolin-1 and cellular processes
- Endoplasmic Reticulum Stress and Disease
- Glycosylation and Glycoproteins Research
- Research on Leishmaniasis Studies
- Sesquiterpenes and Asteraceae Studies
- Virus-based gene therapy research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Developmental Biology and Gene Regulation
- Lipid metabolism and biosynthesis
- Metabolism, Diabetes, and Cancer
- Hippo pathway signaling and YAP/TAZ
- Plant Molecular Biology Research
- Insect-Plant Interactions and Control
University of Nottingham
2015-2024
Max Planck Institute for Chemical Ecology
2024
Queen's Medical Centre
2018-2023
University of North Carolina at Chapel Hill
2023
The Barbara Ann Karmanos Cancer Institute
2023
Wayne State University
2023
Michigan State University
2023
Apogee Biotechnology (United States)
2005-2006
Hershey (United States)
2006
Pennsylvania State University
2000-2004
Abstract N-myristoyltransferases (NMT) add myristate to the NH2 termini of certain proteins, thereby regulating their localization and/or biological function. Using RNA interference, this study functionally characterizes two NMT isozymes in human cells. Unique small interfering RNAs (siRNA) for each isozyme were designed and shown decrease NMT1 or NMT2 protein levels by at least 90%. Ablation inhibited cell replication associated with a loss activation c-Src its target FAK as well reduction...
Abstract The covalent attachment of palmitate to specific proteins by the action palmitoyl acyltransferases (PAT) plays critical roles in biological activities several oncoproteins. Two PAT are expressed human cells: type 1 PATs that modify farnesyl-dependent palmitoylation motif found H- and N-Ras, 2 myristoyl-dependent Src family tyrosine kinases. We have previously shown HIP14 causes cellular transformation. In current study, we show mRNA encoding is up-regulated a number types tumors. To...
ELK-1 is a transcription factor involved in ERK-induced cellular proliferation. Here, we show that its transcriptional activity modulated by ubiquitination at lysine 35 (K35). The level of ubiquitinated rises mitogen-deprived cells and falls upon mitogen stimulation or oncogene expression. Ectopic expression USP17, cell cycle-dependent deubiquitinase, decreases up-regulates target-genes with concomitant increase cyclin D1 In contrast, USP17 depletion attenuates ELK-1-dependent gene slows...
The covalent attachment of palmitate to proteins commonly occurs on cysteine residues near either N-myristoylated glycine or C-terminal farnesylated residues. It therefore seems likely that multiple palmitoyl-acyl transferase (PAT) activities exist recognize and modify these distinct palmitoylation motifs. To evaluate this possibility, two synthetic peptides representing motifs, termed MyrGCK(NBD) FarnCNRas(NBD), were used characterize PAT activity under a variety conditions. human tumour...
The phlebotomine sandfly, Lutzomyia longipalpis , a major vector of the Leishmania parasite, uses terpene pheromones to attract conspecifics for mating. Examination L. genome revealed putative synthase (TPS), which—upon heterologous expression in, and purification from, Escherichia coli —yielded functional enzyme. TPS, termed Ll converted geranyl diphosphate (GPP) into mixture monoterpenes with low efficiency, which β-ocimene was product. ( E,E )-farnesyl (FPP) principally produced small...
Abstract In frog and zebrafish, the Mix/Bix family of paired type homeodomain proteins play key roles in specification differentiation mesendoderm. However, mouse, only a single Mix gene ( mMix ) has been identified to date its function is unknown. We have analyzed expression mouse RNA protein embryos, embryoid bodies formed from embryonic stem cells F9 teratocarcinoma cells, as well several differentiated cell types. Expression culture mirrors that where transcribed transiently primitive...
Abstract Purpose: Testosterone suppression in prostate cancer is limited by serious side effects and resistance via restoration of androgen receptor (AR) functionality. ELK1 required for AR-dependent growth various hormone-dependent castration-resistant models. The amino-terminal domain AR docks at two sites on to coactivate essential genes. This study explores the ability small molecules disrupt ELK1–AR interaction spectrum cancer, inhibiting activity a manner that would predict functional...
Leishmaniasis is a debilitating and often fatal neglected tropical disease. Males from sub-populations of the Leishmania-harbouring sandfly, Lutzomyia longipalpis, produce diterpene sex aggregation pheromone, sobralene, for which geranylgeranyl diphosphate (GGPP) likely isoprenoid precursor. We have identified GGPP synthase (lzGGPPS) L. was recombinantly expressed in bacteria purified functional kinetic analysis. In vitro enzymatic assays using LC-MS showed that lzGGPPS an active enzyme,...
Metazoans have multiple ETS paralogues with overlapping or indiscriminate biological functions. Elk-1, one of three mammalian ternary complex factors (TCFs), is a well-conserved, domain-containing transcriptional regulator mitogen-responsive genes that operates in concert serum response factor (SRF). Nonetheless, its genetic role remains unresolved because the elk-1 gene could be deleted from mouse genome seemingly without adverse effect. Here we explored evolution Elk-1 to gain insight into...
Prostate cancer (PCa) growth requires tethering of the androgen receptor (AR) to chromatin by ETS domain transcription factor ELK1 coactivate critical cell proliferation genes. Disruption ELK1–AR complex is a validated potential means therapeutic intervention in PCa. AR associates with coopting its two ERK docking sites, through amino-terminal (A/B domain) AR. Using mammalian two-hybrid assay, we have now functionally mapped amino acids within peptide segments 358–457 and 514–557 A/B as...
Post-translational modifications (PTMs) are important for protein folding and activity, the ability to recreate physiologically relevant PTM profiles on recombinantly-expressed proteins is vital meaningful functional analysis. The ETS transcription factor ELK-1 serves as a paradigm cellular responses mitogens can synergise with androgen receptor promote prostate cancer progression, although in vitro function analyses date have largely overlooked its complex landscapes. We expressed purified...
The mitogen-responsive, ETS-domain transcription factor ELK-1 stimulates the expression of immediate early genes at onset cell cycle and participates in developmental programming. is subject to multiple levels posttranslational control, including phosphorylation, SUMOylation, ubiquitination. Recently, removal monoubiquitin from ETS domain by Ubiquitin Specific Protease USP17 was shown augment transcriptional activity promote proliferation. Here we have used coimmunoprecipitation experiments,...
The androgen receptor (AR) is a crucial coactivator of ELK1 for prostate cancer (PCa) growth, associating with through two peptide segments (358-457 and 514-557) within the amino-terminal domain (NTD) AR. small-molecule antagonist 5-hydroxy-2-(3-hydroxyphenyl)chromen-4-one (KCI807) binds to AR, blocking binding inhibiting PCa growth. We investigated mode interaction KCI807 AR using systematic mutagenesis coupled coactivation assays, testing polypeptide Raman spectroscopy. In full-length...
<p>Supplementary figures #1-#15</p>
<p>Supplementary figures #1-#15</p>
<div>AbstractPurpose:<p>Testosterone suppression in prostate cancer is limited by serious side effects and resistance via restoration of androgen receptor (AR) functionality. ELK1 required for AR-dependent growth various hormone-dependent castration-resistant models. The amino-terminal domain AR docks at two sites on to coactivate essential genes. This study explores the ability small molecules disrupt ELK1–AR interaction spectrum cancer, inhibiting activity a manner that would...
<div>AbstractPurpose:<p>Testosterone suppression in prostate cancer is limited by serious side effects and resistance via restoration of androgen receptor (AR) functionality. ELK1 required for AR-dependent growth various hormone-dependent castration-resistant models. The amino-terminal domain AR docks at two sites on to coactivate essential genes. This study explores the ability small molecules disrupt ELK1–AR interaction spectrum cancer, inhibiting activity a manner that would...