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Articles 1 - 8 of 8
Full-Text Articles in Medicine and Health Sciences
Disruption Of Drosophila Melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated With Altered Developmental Signaling., Takeshi Sasamura, Kenji Matsuno, Mark E Fortini
Disruption Of Drosophila Melanogaster Lipid Metabolism Genes Causes Tissue Overgrowth Associated With Altered Developmental Signaling., Takeshi Sasamura, Kenji Matsuno, Mark E Fortini
Department of Biochemistry and Molecular Biology Faculty Papers
Developmental patterning requires the precise interplay of numerous intercellular signaling pathways to ensure that cells are properly specified during tissue formation and organogenesis. The spatiotemporal function of many developmental pathways is strongly influenced by the biosynthesis and intracellular trafficking of signaling components. Receptors and ligands must be trafficked to the cell surface where they interact, and their subsequent endocytic internalization and endosomal trafficking is critical for both signal propagation and its down-modulation. In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase. …
The Drosophila Eve Insulator Homie Promotes Eve Expression And Protects The Adjacent Gene From Repression By Polycomb Spreading., Miki Fujioka, Guizhi Sun, James B Jaynes
The Drosophila Eve Insulator Homie Promotes Eve Expression And Protects The Adjacent Gene From Repression By Polycomb Spreading., Miki Fujioka, Guizhi Sun, James B Jaynes
Department of Biochemistry and Molecular Biology Faculty Papers
Insulators can block the action of enhancers on promoters and the spreading of repressive chromatin, as well as facilitating specific enhancer-promoter interactions. However, recent studies have called into question whether the activities ascribed to insulators in model transgene assays actually reflect their functions in the genome. The Drosophila even skipped (eve) gene is a Polycomb (Pc) domain with a Pc-group response element (PRE) at one end, flanked by an insulator, an arrangement also seen in other genes. Here, we show that this insulator has three major functions. It blocks the spreading of the eve Pc domain, preventing repression of the …
Consistent Surgeon Evaluations Of Three-Dimensional Rendering Of Pet/Ct Scans Of The Abdomen Of A Patient With A Ductal Pancreatic Mass., Matthew E Wampole, John C Kairys, Edith P Mitchell, Martha L Ankeny, Mathew L Thakur, Eric Wickstrom
Consistent Surgeon Evaluations Of Three-Dimensional Rendering Of Pet/Ct Scans Of The Abdomen Of A Patient With A Ductal Pancreatic Mass., Matthew E Wampole, John C Kairys, Edith P Mitchell, Martha L Ankeny, Mathew L Thakur, Eric Wickstrom
Department of Biochemistry and Molecular Biology Faculty Papers
Two-dimensional (2D) positron emission tomography (PET) and computed tomography (CT) are used for diagnosis and evaluation of cancer patients, requiring surgeons to look through multiple planar images to comprehend the tumor and surrounding tissues. We hypothesized that experienced surgeons would consistently evaluate three-dimensional (3D) presentation of CT images overlaid with PET images when preparing for a procedure. We recruited six Jefferson surgeons to evaluate the accuracy, usefulness, and applicability of 3D renderings of the organs surrounding a malignant pancreas prior to surgery. PET/CT and contrast-enhanced CT abdominal scans of a patient with a ductal pancreatic mass were segmented into 3D …
G Protein-Coupled Receptor Kinase 2 (Grk2) Is Localized To Centrosomes And Mediates Epidermal Growth Factor-Promoted Centrosomal Separation., Christopher H So, Allison Michal, Konstantin E Komolov, Jiansong Luo, Jeffrey L Benovic
G Protein-Coupled Receptor Kinase 2 (Grk2) Is Localized To Centrosomes And Mediates Epidermal Growth Factor-Promoted Centrosomal Separation., Christopher H So, Allison Michal, Konstantin E Komolov, Jiansong Luo, Jeffrey L Benovic
Department of Biochemistry and Molecular Biology Faculty Papers
G protein-coupled receptor kinases (GRKs) play a central role in regulating receptor signaling, but recent studies suggest a broader role in modulating normal cellular functions. For example, GRK5 has been shown to localize to centrosomes and regulate microtubule nucleation and cell cycle progression. Here we demonstrate that GRK2 is also localized to centrosomes, although it has no role in centrosome duplication or microtubule nucleation. Of interest, knockdown of GRK2 inhibits epidermal growth factor receptor (EGFR)-mediated separation of duplicated centrosomes. This EGFR/GRK2-mediated process depends on the protein kinases mammalian STE20-like kinase 2 (Mst2) and Nek2A but does not involve polo-like kinase …
Leukemia-Associated Rhogef (Larg) Is A Novel Rhogef In Cytokinesis And Required For The Proper Completion Of Abscission., Matthew K Martz, Elda Grabocka, Neil Beeharry, Timothy J Yen, Philip B Wedegaertner
Leukemia-Associated Rhogef (Larg) Is A Novel Rhogef In Cytokinesis And Required For The Proper Completion Of Abscission., Matthew K Martz, Elda Grabocka, Neil Beeharry, Timothy J Yen, Philip B Wedegaertner
Department of Biochemistry and Molecular Biology Faculty Papers
Proper completion of mitosis requires the concerted effort of multiple RhoGEFs. Here we show that leukemia-associated RhoGEF (LARG), a RhoA-specific RGS-RhoGEF, is required for abscission, the final stage of cytokinesis, in which the intercellular membrane is cleaved between daughter cells. LARG colocalizes with α-tubulin at the spindle poles before localizing to the central spindle. During cytokinesis, LARG is condensed in the midbody, where it colocalizes with RhoA. HeLa cells depleted of LARG display apoptosis during cytokinesis with unresolved intercellular bridges, and rescue experiments show that expression of small interfering RNA-resistant LARG prevents this apoptosis. Moreover, live cell imaging of LARG-depleted …
Global Analysis Of Sumo Chain Function Reveals Multiple Roles In Chromatin Regulation., Tharan Srikumar, Megan C Lewicki, Michael Costanzo, Johnny M Tkach, Harm Van Bakel, Kyle Tsui, Erica S Johnson, Grant W Brown, Brenda J Andrews, Charles Boone, Guri Giaever, Corey Nislow, Brian Raught
Global Analysis Of Sumo Chain Function Reveals Multiple Roles In Chromatin Regulation., Tharan Srikumar, Megan C Lewicki, Michael Costanzo, Johnny M Tkach, Harm Van Bakel, Kyle Tsui, Erica S Johnson, Grant W Brown, Brenda J Andrews, Charles Boone, Guri Giaever, Corey Nislow, Brian Raught
Department of Biochemistry and Molecular Biology Faculty Papers
Like ubiquitin, the small ubiquitin-related modifier (SUMO) proteins can form oligomeric "chains," but the biological functions of these superstructures are not well understood. Here, we created mutant yeast strains unable to synthesize SUMO chains (smt3(allR)) and subjected them to high-content microscopic screening, synthetic genetic array (SGA) analysis, and high-density transcript profiling to perform the first global analysis of SUMO chain function. This comprehensive assessment identified 144 proteins with altered localization or intensity in smt3(allR) cells, 149 synthetic genetic interactions, and 225 mRNA transcripts (primarily consisting of stress- and nutrient-response genes) that displayed a >1.5-fold increase in expression levels. This information-rich …
The Tip Of The Tail Needle Affects The Rate Of Dna Delivery By Bacteriophage P22., Justin C Leavitt, Lasha Gogokhia, Eddie B Gilcrease, Anshul Bhardwaj, Gino Cingolani, Sherwood R Casjens
The Tip Of The Tail Needle Affects The Rate Of Dna Delivery By Bacteriophage P22., Justin C Leavitt, Lasha Gogokhia, Eddie B Gilcrease, Anshul Bhardwaj, Gino Cingolani, Sherwood R Casjens
Department of Biochemistry and Molecular Biology Faculty Papers
The P22-like bacteriophages have short tails. Their virions bind to their polysaccharide receptors through six trimeric tailspike proteins that surround the tail tip. These short tails also have a trimeric needle protein that extends beyond the tailspikes from the center of the tail tip, in a position that suggests that it should make first contact with the host's outer membrane during the infection process. The base of the needle serves as a plug that keeps the DNA in the virion, but role of the needle during adsorption and DNA injection is not well understood. Among the P22-like phages are needle …
Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly
Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly
Department of Biochemistry and Molecular Biology Faculty Papers
Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we …