Open Access. Powered by Scholars. Published by Universities.®
- Publication
-
- Department of Biochemistry and Molecular Biology Faculty Papers (3)
- Journal Articles: Biochemistry & Molecular Biology (3)
- Department of Medicine Faculty Papers (2)
- Department of Pathology, Anatomy, and Cell Biology Faculty Papers (1)
- Department of Pharmacology and Experimental Therapeutics Faculty Papers (1)
Articles 1 - 10 of 10
Full-Text Articles in Medicine and Health Sciences
Atomic Structure Of Grk5 Reveals Distinct Structural Features Novel For G Protein-Coupled Receptor Kinases, Konstantin E. Komolov, Anshul Bhardwaj, Jeffrey L. Benovic
Atomic Structure Of Grk5 Reveals Distinct Structural Features Novel For G Protein-Coupled Receptor Kinases, Konstantin E. Komolov, Anshul Bhardwaj, Jeffrey L. Benovic
Department of Biochemistry and Molecular Biology Faculty Papers
G protein-coupled receptor kinases (GRKs) are members of the protein kinase A, G, and C families (AGC) and play a central role in mediating G protein-coupled receptor phosphorylation and desensitization. One member of the family, GRK5, has been implicated in several human pathologies, including heart failure, hypertension, cancer, diabetes, and Alzheimer disease. To gain mechanistic insight into GRK5 function, we determined a crystal structure of full-length human GRK5 at 1.8 Å resolution. GRK5 in complex with the ATP analog 5'-adenylyl β,γ-imidodiphosphate or the nucleoside sangivamycin crystallized as a monomer. The C-terminal tail (C-tail) of AGC kinase domains is a highly …
Isoform- And Species-Specific Control Of Inositol 1,4,5-Trisphosphate (Ip3) Receptors By Reactive Oxygen Species., Száva Bánsághi, Tünde Golenár, Muniswamy Madesh, György Csordás, Satish P. Ramachandrarao, Kumar Sharma, David I Yule, Suresh K Joseph, György Hajnóczky
Isoform- And Species-Specific Control Of Inositol 1,4,5-Trisphosphate (Ip3) Receptors By Reactive Oxygen Species., Száva Bánsághi, Tünde Golenár, Muniswamy Madesh, György Csordás, Satish P. Ramachandrarao, Kumar Sharma, David I Yule, Suresh K Joseph, György Hajnóczky
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Reactive oxygen species (ROS) stimulate cytoplasmic [Ca(2+)] ([Ca(2+)]c) signaling, but the exact role of the IP3 receptors (IP3R) in this process remains unclear. IP3Rs serve as a potential target of ROS produced by both ER and mitochondrial enzymes, which might locally expose IP3Rs at the ER-mitochondrial associations. Also, IP3Rs contain multiple reactive thiols, common molecular targets of ROS. Therefore, we have examined the effect of superoxide anion (O2) on IP3R-mediated Ca(2+) signaling. In human HepG2, rat RBL-2H3, and chicken DT40 cells, we observed [Ca(2+)]c spikes and frequency-modulated oscillations evoked by a O2 donor, xanthine (X) + xanthine oxidase (XO), dose-dependently. …
Expression Of Muc17 Is Regulated By Hif1Α-Mediated Hypoxic Responses And Requires A Methylation-Free Hypoxia Responsible Element In Pancreatic Cancer., Sho Kitamoto, Seiya Yokoyama, Michiyo Higashi, Norishige Yamada, Shyuichiro Matsubara, Sonshin Takao, Surinder K. Batra, Suguru Yonezawa
Expression Of Muc17 Is Regulated By Hif1Α-Mediated Hypoxic Responses And Requires A Methylation-Free Hypoxia Responsible Element In Pancreatic Cancer., Sho Kitamoto, Seiya Yokoyama, Michiyo Higashi, Norishige Yamada, Shyuichiro Matsubara, Sonshin Takao, Surinder K. Batra, Suguru Yonezawa
Journal Articles: Biochemistry & Molecular Biology
MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1α (HIF1α)-dependent pathway in some pancreatic cancer cells (e.g., …
Global Cellular Regulation Including Cardiac Function By Post-Translational Protein Arginylation., Hideko Kaji, Akira Kaji
Global Cellular Regulation Including Cardiac Function By Post-Translational Protein Arginylation., Hideko Kaji, Akira Kaji
Department of Biochemistry and Molecular Biology Faculty Papers
In this issue a very significant contribution to cardiology describing critical roles of ATE1 appears by Kurosaka et al. [1]. In view of this paper, as the discoverers of ATE1, we have been asked to contribute an article (editorial) regarding ATE1 (enzyme which transfers arginine from arginyl tRNA to protein acceptors). This short article consists of three sections: 1) a historical anecdote describing how ATE1 was discovered; 2) its possible role in aging and cellular transformation, and most importantly; 3) its role in the development and maintenance of cardiac activity. The last section has direct bearing to the Kurosaka …
Regulation Of A Duplicated Locus: Drosophila Sloppy Paired Is Replete With Functionally Overlapping Enhancers., Miki Fujioka, James B Jaynes
Regulation Of A Duplicated Locus: Drosophila Sloppy Paired Is Replete With Functionally Overlapping Enhancers., Miki Fujioka, James B Jaynes
Department of Biochemistry and Molecular Biology Faculty Papers
In order to investigate regulation and redundancy within the sloppy paired (slp) locus, we analyzed 30 kilobases of DNA encompassing the tandem, coordinately regulated slp1 and slp2 transcription units. We found a remarkable array of stripe enhancers with overlapping activities surrounding the slp1 transcription unit, and, unexpectedly, glial cell enhancers surrounding slp2. The slp stripe regulatory region generates 7 stripes at blastoderm, and later 14 stripes that persist throughout embryogenesis. Phylogenetic analysis among drosophilids suggests that the multiplicity of stripe enhancers did not evolve through recent duplication. Most of the direct integration among cis-regulatory modules appears to be simply additive, …
Identification Of Thioaptamer Ligand Against E-Selectin: Potential Application For Inflamed Vasculature Targeting., Aman P Mann, Anoma Somasunderam, René Nieves-Alicea, Xin Li, Austin Hu, Anil K Sood, Mauro Ferrari, David G Gorenstein, Takemi Tanaka
Identification Of Thioaptamer Ligand Against E-Selectin: Potential Application For Inflamed Vasculature Targeting., Aman P Mann, Anoma Somasunderam, René Nieves-Alicea, Xin Li, Austin Hu, Anil K Sood, Mauro Ferrari, David G Gorenstein, Takemi Tanaka
Department of Pharmacology and Experimental Therapeutics Faculty Papers
Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA) against E-selectin (ESTA-1) by employing a two-step selection strategy: a recombinant protein-based …
Human Collagen Krox Up-Regulates Type I Collagen Expression In Normal And Scleroderma Fibroblasts Through Interaction With Sp1 And Sp3 Transcription Factors., Magdalini Kypriotou, Gallic Beauchef, Christos Chadjichristos, Russell Widom, Emmanuelle Renard, Sergio A. Jimenez, Joseph Korn, François-Xavier Maquart, Thierry Oddos, Otto Von Stetten, Jean-Pierre Pujol, Philippe Galéra
Human Collagen Krox Up-Regulates Type I Collagen Expression In Normal And Scleroderma Fibroblasts Through Interaction With Sp1 And Sp3 Transcription Factors., Magdalini Kypriotou, Gallic Beauchef, Christos Chadjichristos, Russell Widom, Emmanuelle Renard, Sergio A. Jimenez, Joseph Korn, François-Xavier Maquart, Thierry Oddos, Otto Von Stetten, Jean-Pierre Pujol, Philippe Galéra
Department of Medicine Faculty Papers
Despite several investigations, the transcriptional mechanisms that regulate the expression of both type I collagen genes (COL1A1 and COL1A2) in either physiological or pathological situations, such as scleroderma, are not completely known. We have investigated the role of hc-Krox transcription factor on type I collagen expression by human dermal fibroblasts. hc-Krox exerted a stimulating effect on type I collagen protein synthesis and enhanced the corresponding mRNA steady-state levels of COL1A1 and COL1A2 in foreskin fibroblasts (FF), adult normal fibroblasts (ANF), and scleroderma fibroblasts (SF). Forced hc-Krox expression was found to up-regulate COL1A1 transcription through a -112/-61-bp sequence in FF, ANF, …
Characterization Of Hard2, A Processed Hard1 Gene Duplicate, Encoding A Human Protein N-Alpha-Acetyltransferase., Thomas Arnesen, Matthew J Betts, Frédéric Pendino, David A Liberles, Dave Anderson, Jaime Caro, Xianguo Kong, Jan E Varhaug, Johan R Lillehaug
Characterization Of Hard2, A Processed Hard1 Gene Duplicate, Encoding A Human Protein N-Alpha-Acetyltransferase., Thomas Arnesen, Matthew J Betts, Frédéric Pendino, David A Liberles, Dave Anderson, Jaime Caro, Xianguo Kong, Jan E Varhaug, Johan R Lillehaug
Department of Medicine Faculty Papers
BACKGROUND: Protein acetylation is increasingly recognized as an important mechanism regulating a variety of cellular functions. Several human protein acetyltransferases have been characterized, most of them catalyzing epsilon-acetylation of histones and transcription factors. We recently described the human protein acetyltransferase hARD1 (human Arrest Defective 1). hARD1 interacts with NATH (N-Acetyl Transferase Human) forming a complex expressing protein N-terminal alpha-acetylation activity. RESULTS: We here describe a human protein, hARD2, with 81 % sequence identity to hARD1. The gene encoding hARD2 most likely originates from a eutherian mammal specific retrotransposition event. hARD2 mRNA and protein are expressed in several human cell lines. …
Transcriptional Activation Of The Human Prostatic Acid Phosphatase Gene By Nf-Kappab Via A Novel Hexanucleotide-Binding Site., Stanislav Zelivianski, Richard Glowacki, Ming-Fong Lin
Transcriptional Activation Of The Human Prostatic Acid Phosphatase Gene By Nf-Kappab Via A Novel Hexanucleotide-Binding Site., Stanislav Zelivianski, Richard Glowacki, Ming-Fong Lin
Journal Articles: Biochemistry & Molecular Biology
Human prostatic acid phosphatase (PAcP) is a prostate epithelium-specific differentiation antigen. Cellular PAcP functions as a neutral protein tyrosine phosphatase and is involved in regulating androgen-promoted prostate cancer cell proliferation. Despite the fact that the promoter of the PAcP gene has been cloned, the transcriptional factors that regulate PAcP expression remain unidentified. This article describes our analyses of the promoter of the PAcP gene. Deletion analyses of the promoter sequence up to -4893 (-4893/+87) revealed that a 577 bp fragment (-1356/-779) represents the unique positive cis-active element in human prostate cancer cells but not in HeLa cervix carcinoma cells. Interestingly, …
Genomic Structure Of Murine Mitochondrial Dna Polymerase-Gamma., Justin L. Mott, Grace Denniger, Steve J. Zullo, H. Peter Zassenhaus
Genomic Structure Of Murine Mitochondrial Dna Polymerase-Gamma., Justin L. Mott, Grace Denniger, Steve J. Zullo, H. Peter Zassenhaus
Journal Articles: Biochemistry & Molecular Biology
We have sequenced a genomic clone of the gene encoding the mouse mitochondrial DNA polymerase. The gene consists of 23 exons, which span approximately 13.2 kb, with exons ranging in size from 53 to 768 bp. All intron-exon boundaries conform to the GT-AG rule. By comparison with the human genomic sequence, we found remarkable conservation of the gene structure; the intron-exon borders are in almost identical locations for the 22 introns. The 5' upstream region contains approximately 300 bp of homology between the mouse and human sequences that presumably contain the promoter element. This region lacks any obvious TATA domain …