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Articles 991 - 1020 of 1123
Full-Text Articles in Chemicals and Drugs
Right-Handed 14-Helix In Β3-Peptides From L-Aspartic Acid Monomers, Kamaljit Kaur, Tara Sprules, Wael Soliman, Reem Beleid, Sahar Ahmed
Right-Handed 14-Helix In Β3-Peptides From L-Aspartic Acid Monomers, Kamaljit Kaur, Tara Sprules, Wael Soliman, Reem Beleid, Sahar Ahmed
Pharmacy Faculty Articles and Research
β-Peptides made from L-aspartic acid monomers form a new class of β3-peptides. Here we report the first three-dimensional NMR solution structure of a β3-hexapeptide (1) from L-aspartic acid monomers in 2,2,2-trifluoroethanol (TFE). We show that 1 forms a right-handed 14-helical structure in TFE. α-peptides from naturally occurring L-amino acids adopt a right-handed α-helix whereas β3-peptides formed from β3-amino acids derived from naturally occurring L-amino acids form left-handed 14-helices. The right-handed 14-helical conformation of 1 is a better mimic of α-peptide conformations. Using the NMR structure of 1 in TFE, we …
Alternate Cyclin D1 Mrna Splicing Modulates P27Klp1 Binding And Cell Migration, Zhiping Li, Chenguang Wang, Xuanmao Jiao, Sanjay Katiyar, Mathew C. Casimiro, George C. Prendergast, Michael J. Powell, Richard G. Pestell
Alternate Cyclin D1 Mrna Splicing Modulates P27Klp1 Binding And Cell Migration, Zhiping Li, Chenguang Wang, Xuanmao Jiao, Sanjay Katiyar, Mathew C. Casimiro, George C. Prendergast, Michael J. Powell, Richard G. Pestell
Department of Cancer Biology Faculty Papers
Cyclin D1 is an important cell cycle regulator but in cancer its overexpression also increases cellular migration mediated by p27KlP1 stabilization and RhoA inhibition. Recently, a common polymorphism at the exon 4-intron 4 boundary of the human cyclin D1 gene within a splice donor region was associated with an altered risk of developing cancer. Altered RNA splicing caused by this polymorphism gives rise to a variant cyclin D1 isoform termed cyclin D1b, which has the same N-terminus as the canonical cyclin D1a isoform but a distinct C-terminus. In this study we show that these different isoforms have unique properties …
A Novel And Generalizable Organotypic Slice Platform To Evaluate Stem Cell Potential For Targeting Pediatric Brain Tumors., Shengwen Calvin Li, William Gunter Loudon
A Novel And Generalizable Organotypic Slice Platform To Evaluate Stem Cell Potential For Targeting Pediatric Brain Tumors., Shengwen Calvin Li, William Gunter Loudon
Department of Cancer Biology Faculty Papers
Brain tumors are now the leading cause of cancer-related deaths in children under age 15. Malignant gliomas are, for all practical purposes, incurable and new therapeutic approaches are desperately needed. One emerging strategy is to use the tumor tracking capacity inherent in many stem cell populations to deliver therapeutic agents to the brain cancer cells. Current limitations of the stem cell therapy strategy include that stem cells are treated as a single entity and lack of uniform technology is adopted for selection of clinically relevant sub-populations of stem cells. Specifically, therapeutic success relies on the selection of a clinically competent …
Adenylyl Cyclase Type 6 Overexpression Selectively Enhances Ss-Adrenergic And Prostacyclin Receptor Mediated Inhibition Of Rat Cardiac Fibroblast Function Due To Co-Localization In Lipid Rafts, Xiaoqiu Liu, Muthusamy Thangavel, Shu Qiang Sun, Joseph Kaminsky, Penden Mahautmr, Jeremiah Stitham, John Hwa, Rennolds S. Ostrom
Adenylyl Cyclase Type 6 Overexpression Selectively Enhances Ss-Adrenergic And Prostacyclin Receptor Mediated Inhibition Of Rat Cardiac Fibroblast Function Due To Co-Localization In Lipid Rafts, Xiaoqiu Liu, Muthusamy Thangavel, Shu Qiang Sun, Joseph Kaminsky, Penden Mahautmr, Jeremiah Stitham, John Hwa, Rennolds S. Ostrom
Pharmacy Faculty Articles and Research
Cardiac fibroblasts produce and degrade extracellular matrix and are critical in regulating cardiac remodeling and hypertrophy. Fibroblasts are activated by factors such as transforming growth factor β and inhibited by agents that elevate 3′,5′-cyclic adenosine monophosphate (cAMP) levels. cAMP signal generation and response is known to be compartmentalized in many cell types in part through the colocalization of receptors and specific adenylyl cyclase isoforms in lipid rafts and caveolae. The present study sought to define the localization of key G protein-coupled receptors with adenylyl cyclase type 6 (AC6) in lipid rafts of rat cardiac fibroblasts and to determine if this …
Synthesis And In Vitro Characterization Of Novel Dextran- Methylprednisolone Conjugates With Peptide Linkers: Effects Of Linker Length On Hydrolytic And Enzymatic Release Of Methylprednisolone And Its Peptidyl Intermediates, Suman Penugonda, Anil Kumar, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar
Synthesis And In Vitro Characterization Of Novel Dextran- Methylprednisolone Conjugates With Peptide Linkers: Effects Of Linker Length On Hydrolytic And Enzymatic Release Of Methylprednisolone And Its Peptidyl Intermediates, Suman Penugonda, Anil Kumar, Hitesh K. Agarwal, Keykavous Parang, Reza Mehvar
Pharmacy Faculty Articles and Research
To control the rate of release of methylprednisolone (MP) in lysosomes, new dextran-MP conjugates with peptide linkers were synthesized and characterized. Methylprednisolone succinate (MPS) was attached to dextran 25 kDa using linkers with 1-5 Gly residues. The release characteristics of the conjugates in pH 4.0 and 7.4 buffers, blood, liver lysosomes, and various lysosomal proteinases were determined using a size-exclusion and/or a newly developed reversed-phase HPLC method capable of simultaneous quantitation of MP, MPS, and all five possible MPS-peptidyl intermediates. We synthesized conjugates with >= 90% purity and 6.9-9.5% (w/w) degree of MP substitution. The conjugates were stable at pH …
Acetylation In Nuclear Receptor Signaling And The Role Of Sirtuins, Chenguang Wang, Michael J. Powell, Vladimir M. Popov, Richard G. Pestell
Acetylation In Nuclear Receptor Signaling And The Role Of Sirtuins, Chenguang Wang, Michael J. Powell, Vladimir M. Popov, Richard G. Pestell
Department of Cancer Biology Faculty Papers
It has been known since the early 1970s that nuclear receptor complexes bind DNA in association with co-regulatory proteins. Characterization of these nuclear receptor coregulators has revealed diverse enzymatic activities which temporally and spatially coordinate nuclear receptor activity within the context of local chromatin in response to diverse hormone signals. Chromatin modifying proteins, which dictate the higher order chromatin structure in which DNA is packaged, in turn orchestrate orderly recruitment of nuclear receptor complexes. Modifications of histones include acetylation, methylation, phosphorylation, ubiquitylation, sumoylation, ADP ribosylation, deimination and proline isomerization (1). At this time, we understand how a subset of these …
Common And Distinct Mechanisms Of Different Redox-Active Carcinogens Involved In The Transformation Of Mouse Jb6p+ Cells, Sun Yang, Bobbye J. Misner, Rita Chiu, Frank L. Meyskens Jr.
Common And Distinct Mechanisms Of Different Redox-Active Carcinogens Involved In The Transformation Of Mouse Jb6p+ Cells, Sun Yang, Bobbye J. Misner, Rita Chiu, Frank L. Meyskens Jr.
Pharmacy Faculty Articles and Research
We transformed JB6P+ cells with prolonged intermittent low-dose UVB radiation or prolonged exposure to low-dose H2O2 or CdCl2. Stable transformation was confirmed by an anchorage-independence assay. The JB6P+ transformants formed more colonies (∼six folds) in soft agar as compared to their JB6P+ parent cells and were associated with increased intracellular reactive oxygen species (ROS) levels. Activating protein-1 (AP-1) is a family of transcription factors that are rapidly activated by elevated intracellular ROS levels, and their composition is important in the process of cellular transformation and/or tumor progression. To investigate if carcinogenesis induced by distinct carcinogens was via similar molecular mechanisms …
Localization Of A Microsporidia Adam (A Disintegrin And Metalloprotease Domain) Protein And Identification Of Potential Binding Partners., Carrie E. Jolly
Localization Of A Microsporidia Adam (A Disintegrin And Metalloprotease Domain) Protein And Identification Of Potential Binding Partners., Carrie E. Jolly
Electronic Theses and Dissertations
Microsporidia are spore-forming, obligate intracellular pathogens typically associated with opportunistic infections in immunocompromised individuals. Treatment options for microsporidia infections in humans are limited and additional research is necessary to create better therapeutic agents. For many pathogenic organisms, adhesion to the host cell surface is a prerequisite for tissue colonization and invasion. Our previous research has demonstrated a direct relationship between adherence of microsporidia spores to the surface of host cells and infectivity in vitro. In an effort to better understand adherence, we have turned our attention to determining what proteins may be involved in this process. Examination of the …
The Role Of Multi-Drug Resistance Associated Protein 4 And P-Glycoprotein In Resistance Of Neuroblastoma To Topotecan And Irinotecan, Patricia Kellie Turner
The Role Of Multi-Drug Resistance Associated Protein 4 And P-Glycoprotein In Resistance Of Neuroblastoma To Topotecan And Irinotecan, Patricia Kellie Turner
Theses and Dissertations (ETD)
High-risk neuroblastoma presents a significant therapeutic challenge because the 5-year survival rate remains less than 30% despite the use of surgery, multi-agent chemotherapy, radiation, and autologous bone marrow transplant. Novel therapeutic modalities are under development. The camptothecin analogs topotecan and irinotecan have been identified as successful cytotoxic agents. For topotecan, pharmacokinetically guided dosing to achieve a systemic exposure associated with preclinical anti-tumor activity in neuroblastoma xenograft models is feasible and has elicited favorable responses in children with high-risk neuroblastoma. However, some children with high-risk disease did not respond to the putatively effective topotecan systemic exposure. These children represent a subset …
Micro Rna 145 Targets The Insulin Receptor Substrate-1 And Inhibits The Growth Of Colon Cancer Cells, Bin Shi, Laura Sepp-Lorenzino, Marco Prisco, Peter Linsley, Tiziana Deangelis, Renato Baserga
Micro Rna 145 Targets The Insulin Receptor Substrate-1 And Inhibits The Growth Of Colon Cancer Cells, Bin Shi, Laura Sepp-Lorenzino, Marco Prisco, Peter Linsley, Tiziana Deangelis, Renato Baserga
Department of Cancer Biology Faculty Papers
The insulin receptor substrate-1 (IRS-1), a docking protein for both the type 1 insulin-like growth factor receptor (IGF-IR) and the insulin receptor, is known to send a mitogenic, anti-apoptotic, and anti-differentiation signal. Several micro RNAs (miRs) are suggested by the data base as possible candidates for targeting IRS-1. We show here that one of the miRs predicted by the data base, miR145, whether transfected as a synthetic oligonucleotide or expressed from a plasmid, causes down-regulation of IRS-1 in human colon cancer cells. IRS-1 mRNA is not decreased by miR145, while it is down-regulated by an siRNA targeting IRS-1. Targeting of …
Sirtuins, Nuclear Hormone Receptor Acetylation And Transcriptional Regulation, James R. Whittle, Michael J. Powell, Vladimir M. Popov, L. Andrew Shirley, Chenguang Wang, Richard G. Pestell
Sirtuins, Nuclear Hormone Receptor Acetylation And Transcriptional Regulation, James R. Whittle, Michael J. Powell, Vladimir M. Popov, L. Andrew Shirley, Chenguang Wang, Richard G. Pestell
Department of Cancer Biology Faculty Papers
Endocrine signaling via nuclear receptors (NRs) is known to play an important role in normal physiology as well as in human tumor progression. Hormones regulate gene expression by altering local chromatin structure and, thereby, accessibility of transcriptional co-regulators to DNA. Recently it has been shown that non-histone proteins involved in hormone signaling, such as nuclear receptors and NR co-activators, are regulated by acetylation, resulting in their altered transcriptional activity. NAD-dependent protein deacetylases, the sirtuins (Sir2-related enzymes), directly modify NRs. Because sirtuins have been shown to regulate tumor cellular growth, aging, metabolic signaling and endocrine hormone signaling, they might play a …
Phenylalanyl-Trna Synthetase Editing Defects Result In Efficient Mistranslation Of Phenylalanine Codons As Tyrosine, Jiqiang Ling, Srujana S. Yadavalli, Michael Ibba
Phenylalanyl-Trna Synthetase Editing Defects Result In Efficient Mistranslation Of Phenylalanine Codons As Tyrosine, Jiqiang Ling, Srujana S. Yadavalli, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Translational quality control is monitored at several steps, including substrate selection by aminoacyl-tRNA synthetases (aaRSs), and discrimination of aminoacyl-tRNAs by elongation factor Tu (EF-Tu) and the ribosome. Phenylalanyl-tRNA synthetase (PheRS) misactivates Tyr but is able to correct the mistake using a proofreading activity named editing. Previously we found that overproduction of editing-defective PheRS resulted in Tyr incorporation at Phe-encoded positions in vivo , although the misreading efficiency could not be estimated. This raised the question as to whether or not EF-Tu and the ribosome provide further proofreading mechanisms to prevent mistranslation of Phe codons by Tyr. Here we show that, …
An Aminoacyl-Trna Synthetase: Elongation Factor Complex For Substrate Channeling In Archaeal Translation, Corinne D. Hausmann, Mette Praetorius-Ibba, Michael Ibba
An Aminoacyl-Trna Synthetase: Elongation Factor Complex For Substrate Channeling In Archaeal Translation, Corinne D. Hausmann, Mette Praetorius-Ibba, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Translation requires the specific attachment of amino acids to tRNAs by aminoacyl-tRNA synthetases (aaRSs) and the subsequent delivery of aminoacyl-tRNAs to the ribosome by elongation factor 1 alpha (EF-1α). Interactions between EF-1α and various aaRSs have been described in eukaryotes, but the role of these complexes remains unclear. To investigate possible interactions between EF-1α and other cellular components, a yeast two-hybrid screen was performed for the archaeon Methanothermobacter thermautotrophicus. EF-1α was found to form a stable complex with leucyl-tRNA synthetase (LeuRS; KD = 0.7 μ M). Complex formation had little effect on EF-1α activity, but increased the kcat …
Stabilization Of Smar1 Mrna By Pga2 Involves A Stem Loop Structure In The 5' Utr, Lakshminarasimhan Pavritha, Shravanti Rampalli, Surajit Sinha, Kadreppa Sreenath, Richard G. Pestell, Samit Chattopadhyay
Stabilization Of Smar1 Mrna By Pga2 Involves A Stem Loop Structure In The 5' Utr, Lakshminarasimhan Pavritha, Shravanti Rampalli, Surajit Sinha, Kadreppa Sreenath, Richard G. Pestell, Samit Chattopadhyay
Department of Cancer Biology Faculty Papers
Prostaglandins are anticancer agents known to inhibit tumor cell proliferation both in vitro and in vivo by affecting the mRNA stability. Here we report that a MAR-binding protein SMAR1 is a target of Prostaglandin A2 (PGA2) induced growth arrest. We identify a regulatory mechanism leading to stabilization of SMAR1 transcript. Our results show that a minor stem and loop structure present in the 5' UTR of SMAR1 (1-UTR) is critical for nucleoprotein complex formation that leads to SMAR1 stabilization in response to PGA2. This results in an increased SMAR1 transcript and altered protein levels, that in turn causes downregulation of …
Plant-Derived Epcam Antigen Induces Protective Anti-Cancer Response., Robert Brodzik, Sergei Spitsin, Max Golovkin, Katarzyna Bandurska, Carla Portocarrero, Monika Okulicz, Zenon Steplewski, Hilary Koprowski
Plant-Derived Epcam Antigen Induces Protective Anti-Cancer Response., Robert Brodzik, Sergei Spitsin, Max Golovkin, Katarzyna Bandurska, Carla Portocarrero, Monika Okulicz, Zenon Steplewski, Hilary Koprowski
Department of Cancer Biology Faculty Papers
Immunotherapy holds great promise for treatment of infectious and malignant diseases and might help to prevent the occurrence and recurrence of cancer. We produced a plant-derived tumor-associated colorectal cancer antigen EpCAM (pGA733) at high yields using two modern plant expression systems. The full antigenic domain of EpCAM was efficiently purified to confirm its antigenic and immunogenic properties as compared to those of the antigen expressed in the baculovirus system (bGA733). Recombinant plant-derived antigen induced a humoral immune response in BALB/c mice. Sera from those mice efficiently inhibited the growth of SW948 colorectal carcinoma cells xenografted in nude mice, as compared …
Autocrine Prolactin Promotes Prostate Cancer Cell Growth Via Janus Kinase-2-Signal Transducer And Activator Of Transcription-5a/B Signaling Pathway., Ayush Dagvadorj, Sean Collins, Jean-Baptiste Jomain, Junaid Abdulghani, James Karras, Tobias Zellweger, Hongzhen Li, Martti Nurmi, Kalle Alanen, Tuomas Mirtti, Tapio Visakorpi, Lukas Bubendorf, Vincent Goffin, Marja T Nevalainen
Autocrine Prolactin Promotes Prostate Cancer Cell Growth Via Janus Kinase-2-Signal Transducer And Activator Of Transcription-5a/B Signaling Pathway., Ayush Dagvadorj, Sean Collins, Jean-Baptiste Jomain, Junaid Abdulghani, James Karras, Tobias Zellweger, Hongzhen Li, Martti Nurmi, Kalle Alanen, Tuomas Mirtti, Tapio Visakorpi, Lukas Bubendorf, Vincent Goffin, Marja T Nevalainen
Department of Cancer Biology Faculty Papers
The molecular mechanisms that promote progression of localized prostate cancer to hormone-refractory and disseminated disease are poorly understood. Prolactin (Prl) is a local growth factor produced in high-grade prostate cancer, and exogenously added Prl in tissue or explant cultures of normal and malignant prostate is a strong mitogen and survival factor for prostate epithelium. The key signaling proteins that mediate the biological effects of Prl in prostate cancer are Signal Transducer and Activator of Transcription (Stat)-5a/5b via activation of Janus kinase-2. Importantly, inhibition of Stat5a/b in prostate cancer cells induces apoptotic death. Using a specific Prl receptor antagonist (Delta1-9G129R-hPRL), we …
Smallpox Subunit Vaccine Produced In Planta Confers Protection In Mice, Maxim Golovkin, Sergei Spitsin, Vyacheslav Andrianov, Yuriy Smirnov, Yuhong Xiao, Natalia Pogrebnyak, Karen Markley, Robert Brodzik, Yuri Gleba, Stuart N Isaacs, Hilary Koprowski
Smallpox Subunit Vaccine Produced In Planta Confers Protection In Mice, Maxim Golovkin, Sergei Spitsin, Vyacheslav Andrianov, Yuriy Smirnov, Yuhong Xiao, Natalia Pogrebnyak, Karen Markley, Robert Brodzik, Yuri Gleba, Stuart N Isaacs, Hilary Koprowski
Department of Cancer Biology Faculty Papers
We report here the in planta production of the recombinant vaccinia virus B5 antigenic domain (pB5), an attractive component of a subunit vaccine against smallpox. The antigenic domain was expressed by using efficient transient and constitutive plant expression systems and tested by various immunization routes in two animal models. Whereas oral administration in mice or the minipig with collard-derived insoluble pB5 did not generate an anti-B5 immune response, intranasal administration of soluble pB5 led to a rise of B5-specific immunoglobulins, and parenteral immunization led to a strong anti-B5 immune response in both mice and the minipig. Mice immunized i.m. with …
Stability Of Eukaryotic Elongation Factor One Alpha Protein In The Cell, Jennifer Watry
Stability Of Eukaryotic Elongation Factor One Alpha Protein In The Cell, Jennifer Watry
Honors Theses
Eukaryotic Elongation Factor One Alpha (eEF1A) is an abundant protein found in every cell of every organism and is involved in functions concerning protein synthesis and degradation, the cytoskeleton, and signaling. How these functions are regulated is not yet understood for this protein. Regulation of the protein may be controlled by transcription of the genes encoding the protein or the stability and modification of the protein. The goal of this project was to determine the stability of eEf1A proteins in Arabidopsis thaliana. Protein stability was determined by treating tissues with cycloheximide, an inhibitor of protein synthesis. Gel electrophoresis and …
Cell Fate Determination Factor Dach1 Inhibits C-Jun-Induced Contact-Independent Growth, Kongming Wu, Manran Liu, Anping Li, Howard Donninger, Mahadev Rao, Xuanmao Jiao, Michael P. Lisanti, Ales Cvekl, Michael Birrer, Richard G. Pestell
Cell Fate Determination Factor Dach1 Inhibits C-Jun-Induced Contact-Independent Growth, Kongming Wu, Manran Liu, Anping Li, Howard Donninger, Mahadev Rao, Xuanmao Jiao, Michael P. Lisanti, Ales Cvekl, Michael Birrer, Richard G. Pestell
Department of Cancer Biology Faculty Papers
The cell fate determination factor DACH1 plays a key role in cellular differentiation in metazoans. DACH1 is engaged in multiple context-dependent complexes that activate or repress transcription. DACH1 can be recruited to DNA via the Six1/Eya bipartite transcription (DNA binding/coactivator) complex. c-Jun is a critical component of the activator protein (AP)-1 transcription factor complex and can promote contact-independent growth. Herein, DACH1 inhibited c-Jun-induced DNA synthesis and cellular proliferation. Excision of c-Jun with Cre recombinase, in c-jun(f1/f1) 3T3 cells, abrogated DACH1-mediated inhibition of DNA synthesis. c-Jun expression rescued DACH1-mediated inhibition of cellular proliferation. DACH1 inhibited induction of c-Jun by physiological stimuli …
The Association Between Lifestyle Factors And Inflammatory Markers, Kerry Ann Stonebrook
The Association Between Lifestyle Factors And Inflammatory Markers, Kerry Ann Stonebrook
Loma Linda University Electronic Theses, Dissertations & Projects
Background: Cardiovascular disease (CVD) is the leading cause of death for both men and women in the United States. While smoking, high blood pressure, and elevated cholesterol levels are established risk factors for CVD, inflammation is being evaluated as a potential independent risk factor. A key cytokine regulator of the inflammatory response, interleukin-1 (IL-1), has emerged as playing a particularly important role at the genetic level in determining the degree to which the inflammation pathway is turned on. How an individual’s genetic make-up affects inflammation, CVD risk, and response to lifestyle intervention is an area of research that is in …
The Functional Significance Of Nuclear Receptor Acetylation., Vladimir M. Popov, Chenguang Wang, L . Andrew Shirley, Anne Rosenberg, Shengwen Li, Marja Nevalainen, Maofu Fu, Richard G. Pestell
The Functional Significance Of Nuclear Receptor Acetylation., Vladimir M. Popov, Chenguang Wang, L . Andrew Shirley, Anne Rosenberg, Shengwen Li, Marja Nevalainen, Maofu Fu, Richard G. Pestell
Department of Cancer Biology Faculty Papers
The endocrine signaling governing nuclear receptor (NR) function has been known for several decades to play a crucial role in the onset and progression of several tumor types. Notably among these are the estrogen receptor (ER) in breast cancer and androgen receptor (AR) in prostate cancer. Other nuclear receptors may be involved in cancer progression including the peroxisome-proliferator activating receptor gamma (PPARgamma), which has been implicated in breast, thyroid, and colon cancers. These NR are phylogenetically conserved modular transcriptional regulators, which like histones, undergo post-translational modification by acetylation, phosphorylation and ubiquitination. Importantly, the transcriptional activity of the receptors is governed …
Somatic Excision Demonstrates That C-Jun Induces Cellular Migration And Invasion Through Induction Of Stem Cell Factor, Sanjay Katiyar, Xuanmao Jiao, Erwin Wagner, Michael P. Lisanti, Richard G. Pestell
Somatic Excision Demonstrates That C-Jun Induces Cellular Migration And Invasion Through Induction Of Stem Cell Factor, Sanjay Katiyar, Xuanmao Jiao, Erwin Wagner, Michael P. Lisanti, Richard G. Pestell
Department of Cancer Biology Faculty Papers
Cancer cells arise through sequential acquisition of mutations in tumor suppressors and oncogenes. c-Jun, a critical component of the AP-1 complex, is frequently overexpressed in diverse tumor types and has been implicated in promoting cellular proliferation, migration, and angiogenesis. Functional analysis of candidate genetic targets using germ line deletion in murine models can be compromised through compensatory mechanisms. As germ line deletion of c-jun induces embryonic lethality, somatic deletion of the c-jun gene was conducted using floxed c-jun (c-junf/f) conditional knockout mice. c-jun-deleted cells showed increased cellular adhesion, stress fiber formation, and reduced cellular migration. The reduced migratory …
Protein Pyrophosphorylation By Inositol Pyrophosphates Is A Posttranslational Event, Rashna Bhandari, Adolfo Saiardi, Yousef Ahmadibeni, Adele M. Snowman, Adam C. Resnick, Troels Z. Kristiansen, Henrik Molina, Akhilesh Pandey, J. Kent Werner Jr., Krishna R. Juluri, Yong Xu, Glenn D. Prestwich, Keykavous Parang, Solomon H. Snyder
Protein Pyrophosphorylation By Inositol Pyrophosphates Is A Posttranslational Event, Rashna Bhandari, Adolfo Saiardi, Yousef Ahmadibeni, Adele M. Snowman, Adam C. Resnick, Troels Z. Kristiansen, Henrik Molina, Akhilesh Pandey, J. Kent Werner Jr., Krishna R. Juluri, Yong Xu, Glenn D. Prestwich, Keykavous Parang, Solomon H. Snyder
Pharmacy Faculty Articles and Research
In a previous study, we showed that the inositol pyrophosphate diphosphoinositol pentakisphosphate (IP(7)) physiologically phosphorylates mammalian and yeast proteins. We now report that this phosphate transfer reflects pyrophosphorylation. Thus, proteins must be prephosphorylated by ATIP to prime them for IP(7) phosphorylation. IP(7) phosphorylates synthetic phosphopeptides but not if their phosphates have been masked by methylation or pyrophosphorylation. Moreover, IP(7) phosphorylated peptides are more acid-labile and more resistant to phosphatases than ATIP phosphorylated peptides, indicating a different type of phosphate bond. Pyrophosphorylation may represent a novel mode of signaling to proteins.
Coupling Coherence Distinguishes Structure Sensitivity In Protein Electron Transfer, Tatiana Prytkova, Igor V. Kurnikov, David Beratan
Coupling Coherence Distinguishes Structure Sensitivity In Protein Electron Transfer, Tatiana Prytkova, Igor V. Kurnikov, David Beratan
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Quantum mechanical analysis of electron tunneling in nine thermally fluctuating cytochrome b562 derivatives reveals two distinct protein-mediated coupling limits. A structure-insensitive regime arises for redox partners coupled through dynamically averaged multiple-coupling pathways (in seven of the nine derivatives) where heme-edge coupling leads to the multiple-pathway regime. A structure-dependent limit governs redox partners coupled through a dominant pathway (in two of the nine derivatives) where axial-ligand coupling generates the single-pathway limit and slower rates. This two-regime paradigm provides a unified description of electron transfer rates in 26 ruthenium-modified heme and blue-copper proteins, as well as in numerous photosynthetic proteins.
Flavin Charge Transfer Transitions Assist Dna Photolyase Electron Transfer, Spiros S. Skourtis, Tatiana Prytkova, David Beratan
Flavin Charge Transfer Transitions Assist Dna Photolyase Electron Transfer, Spiros S. Skourtis, Tatiana Prytkova, David Beratan
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
This contribution describes molecular dynamics, semi-empirical and ab-initio studies of the primary photo-induced electron transfer reaction in DNA photolyase. DNA photolyases are FADH−-containing proteins that repair UV-damaged DNA by photo-induced electron transfer. A DNA photolyase recognizes and binds to cyclobutatne pyrimidine dimer lesions of DNA. The protein repairs a bound lesion by transferring an electron to the lesion from FADH−, upon photo-excitation of FADH− with 350–450 nm light. We compute the lowest singlet excited states of FADH− in DNA photolyase using INDO/S configuration interaction, time-dependent density-functional, and time-dependent Hartree-Fock methods. The calculations identify the lowest singlet excited state of FADH− …
Functional Association Between Three Archaeal Aminoacyl-Trna Synthetases, Mette Praetorius-Ibba, Corinne D. Hausmann, Molly Paras, Theresa E. Rogers, Michael Ibba
Functional Association Between Three Archaeal Aminoacyl-Trna Synthetases, Mette Praetorius-Ibba, Corinne D. Hausmann, Molly Paras, Theresa E. Rogers, Michael Ibba
Biology, Chemistry, and Environmental Sciences Faculty Articles and Research
Aminoacyl-tRNA synthetases (aaRSs) are responsible for attaching amino acids to their cognate tRNAs during protein synthesis. In eukaryotes aaRSs are commonly found in multi-enzyme complexes, although the role of these complexes is still not completely clear. Associations between aaRSs have also been reported in archaea, including a complex between prolyl-(ProRS) and leucyl-tRNA synthetases (LeuRS) in Methanothermobacter thermautotrophicus that enhances tRNAPro aminoacylation. Yeast two-hybrid screens suggested that lysyl-tRNA synthetase (LysRS) also associates with LeuRS in M. thermautotrophicus. Co-purification experiments confirmed that LeuRS, LysRS, and ProRS associate in cell-free extracts. LeuRS bound LysRS and ProRS with a comparable KD …
Tyrosine Phosphorylation Of Villin: Effects On Actin Dynamics, Cell Morphology And Cell Migration, Alok Tomar
Tyrosine Phosphorylation Of Villin: Effects On Actin Dynamics, Cell Morphology And Cell Migration, Alok Tomar
Theses and Dissertations (ETD)
Cell migration is a key aspect of many normal and abnormal biological processes, including embryonic development, defense against infections, wound healing, and tumor cell metastasis. In this study we demonstrate that an epithelial cell actin-binding protein, villin, plays a crucial role in the process of cell migration. Overexpression of villin in doxycyline-regulated HeLa Tet-off and MDCK Tet-off cells enhanced cell migration. We further demonstrate that tyrosine phosphorylation of villin by c-src is required for villin-induced cell migration. Previously, we identified four tyrosine phosphorylation sites in the amino-terminal domain of villin. I further identified six new sites in the carboxylterminal region …
Epigenetics And The Estrogen Receptor, Jennifer E. Leader, Chenuang Wang, Vladimir M. Popov, Maofu Fu, Richard G. Pestell
Epigenetics And The Estrogen Receptor, Jennifer E. Leader, Chenuang Wang, Vladimir M. Popov, Maofu Fu, Richard G. Pestell
Department of Cancer Biology Faculty Papers
The position effect variegation in Drosophila and Schizosaccharomyces pombe, and higher-order chromatin structure regulation in yeast, is orchestrated by modifier genes of the Su(var) group, (e.g., histone deacetylases ([HDACs]), protein phosphatases) and enhancer E(Var) group (e.g., ATP [adenosine 5'-triphosphate]-dependent nucleosome remodeling proteins). Higher-order chromatin structure is regulated in part by covalent modification of the N-terminal histone tails of chromatin, and histone tails in turn serve as platforms for recruitment of signaling modules that include nonhistone proteins such as heterochromatin protein (HP1) and NuRD. Because the enzymes governing chromatin structure through covalent modifications of histones (acetylation, methylation, phosphorylation, ubiquitination) can also …
Gene Expression In The Mouse Placenta: Developmental And Stress Responses, Ciprian P. Gheorghe
Gene Expression In The Mouse Placenta: Developmental And Stress Responses, Ciprian P. Gheorghe
Loma Linda University Electronic Theses, Dissertations & Projects
Successful placental development is crucial for optimal growth, maturation, and survival of the embryo/fetus. Placental failure and placental pathology contributes to both morbidity and mortality of the fetus. We sought to understand normal placental development and also placental responses to stress using oligonucleotide microarray technology. To examine genetic aspects of normal placental development, we investigated gene expression patterns in the murine placenta at embryonic day 10.5 (E10.5), E12.5, E15.5, and E17.5. Hypoxia has been identified as a major stressor in placental and fetal development. In order to comprehend more completely hypoxic stress responses we sought to measure gene expression changes …
Cyclin D1 Repression Of Nuclear Respiratory Factor 1 Integrates Nuclear Dna Synthesis And Mitochondrial Function., Chenguang Wang, Zhiping Li, Yinan Lu, Runlei Du, Sanjay Katiyar, Jianguo Yang, Maofu Fu, Jennifer E Leader, Andrew Quong, Phyllis M Novikoff, Richard Pestell
Cyclin D1 Repression Of Nuclear Respiratory Factor 1 Integrates Nuclear Dna Synthesis And Mitochondrial Function., Chenguang Wang, Zhiping Li, Yinan Lu, Runlei Du, Sanjay Katiyar, Jianguo Yang, Maofu Fu, Jennifer E Leader, Andrew Quong, Phyllis M Novikoff, Richard Pestell
Department of Cancer Biology Faculty Papers
Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis and mitochondrial function.