A5067106221- Multiple Myeloma Research and Treatments
- Protein Degradation and Inhibitors
- Monoclonal and Polyclonal Antibodies Research
- Ubiquitin and proteasome pathways
- Glycosylation and Glycoproteins Research
- T-cell and B-cell Immunology
- Quinazolinone synthesis and applications
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Toxin Mechanisms and Immunotoxins
- Peptidase Inhibition and Analysis
- RNA Interference and Gene Delivery
- Histone Deacetylase Inhibitors Research
- Biochemical and Structural Characterization
- Cell Adhesion Molecules Research
- Cancer therapeutics and mechanisms
- Chronic Lymphocytic Leukemia Research
- Cancer Mechanisms and Therapy
- Computational Drug Discovery Methods
- Transgenic Plants and Applications
- Acute Myeloid Leukemia Research
- Genomic variations and chromosomal abnormalities
- Protein Kinase Regulation and GTPase Signaling
- RNA Research and Splicing
- PI3K/AKT/mTOR signaling in cancer
University of Minnesota
2014-2023
Institut thématique Génétique, génomique et bioinformatique
1989-2015
University of Iowa
1985-2013
Pennsylvania State University
2013
Penn State Milton S. Hershey Medical Center
2013
Twin Cities Orthopedics
1991-2007
Mayo Clinic in Arizona
2001
Dana-Farber Cancer Institute
2001
Medical College of Wisconsin
2001
Mayo Clinic
2001
NMR spectral analysis of the novel amino acid, diphthamide, in elongation factor 2 which is ADP-ribosylated by diphtheria toxin suggests that it 2-[3carboxyamido-3-(trimethylammonio)propyl]histidine.Ribosyl-diphthamide was prepared enzymatic hydrolysis ADP-ribosyl-elongation and three compounds were produced its chemical (Van Ness, B. G., Howard, J. B., Bodley, W. (1980) BioL Chem 266,10717-10720).Proton spectroscopy 'HzO diphthine demonstrated elements histidine minus carbon proton plus 14...
elongation factor 2 (EF-2) which is ADP-ribosylated by diphtheria toxin (Robinson, E.
// Ravyn M. Thompson 1 , Dominik Dytfeld 2 Leticia Reyes Reeder Robinson Brittany Smith Yefim Manevich Andrzej Jakubowiak 3 Mieczyslaw Komarnicki Anna Przybylowicz-Chalecka Tomasz Szczepaniak Amit K. Mitra 5 Brian G. Van Ness Magdalena Luczak 4 Nathan Dolloff 1, * Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University South Carolina, Charleston, SC, USA Karol Marcinkowski Sciences, Poznan, Poland Chicago, IL, Institute Bioorganic Chemistry, Polish...
D-Glucose deprivation of primary rat brain glial cell cultures, by incubation with 25 mM D-fructose for 24 h, resulted in a 4-5-fold induction D-glucose transport activity. In contrast, 24-h starvation neuronal cultures had only marginal effect (1.5-2-fold) on Northern blot analysis total cellular RNA demonstrated that under these conditions the cells specifically increased steady-state level transporter mRNA 4-6-fold, whereas revealed no significant alteration amount deprivation. These...
A systematic analysis of the fate DNA between kappa chain variable (V kappa) and joining (J genes in cells that have rearranged loci was carried out. The from a variety kappa-producing plasmacytomas, lambda-producing hybridomas, kappa-expressing lymphocytes digested, fractionated by size, analyzed with two probes containing sequences 5' J kappa. In 13 28 plasmacytomas examined rearrangement V appears to be accompanied loss upstream However, rest one or more are retained new context. 9 12...
Multiple myeloma is a hematologic malignancy characterized by the proliferation of neoplastic plasma cells in bone marrow. Although first-to-market proteasome inhibitor bortezomib (Velcade) has been successfully used to treat patients with myeloma, drug resistance remains an emerging problem. In this study, we identify signatures sensitivity and gene expression profiling (GEP) using pairs bortezomib-sensitive (BzS) bortezomib-resistant (BzR) cell lines created from Bcl-XL/Myc...
Deregulated expression of both Myc and Bcl-XL are consistent features human plasma cell neoplasms (PCNs). To investigate whether targeted in mouse cells might lead to an improved model PCN, we generated transgenics by inserting a single-copy histidine-tagged gene, MycHis, into the Ig heavy-chain Cα locus. We also transgenic mice that contain multicopy Flag-tagged Bcl-xFlag transgene driven κ light-chain 3′ enhancer. Single-transgenic remained tumor free 380 days age, whereas...
DNA fragments containing immunoglobulin kappa-chain sequences from two different plasmacytomas (PC 3609 and PC 7043) were found by blot-hybridization studies to be dissociated germ-line on both the 3' 5' ends. These cloned, sequenced, contain structural features of a product recombination events. Each contained variable (V kappa) gene segment recombined with joining (J followed characteristic kappa light chain V-J reciprocal structure, J flanking sequence joined V sequence. segments...
We have developed a method for the purification in micromole amounts of trypsin-derived ADP-ribosyl peptide from diphtheria toxin-modified yeast elongation factor 2 (EF-2). EF-2 was partially purified (15 to 20% purity) by ammonium sulfate precipitation and DEAE-Sephadex chromatography. After [3H]ADP-ribosylation [3H]nad+ toxin, digested with trypsin homogeneous [3H]ADP-ribosyl isolated chromatography on dihydroxyboryl-substituted cellulose. Based amount ADP-ribose acceptor activity crude...
The MYC proto-oncogene is a transcription factor implicated in broad range of cancers. regulated by several post-translational modifications including SUMOylation, but the functional impact this modification still unclear. Here, we report that SUMO E3 ligase PIAS1 SUMOylates MYC. We demonstrate promotes, SUMOylation-dependent manner, phosphorylation at serine 62 and dephosphorylation threonine 58. These events reduce turnover, leading to increased transcriptional activity. Furthermore, find...
The splicing patterns and sequences of two processed kappa immunoglobulin germ line mRNAs are presented. A 1.1-kilobase (kb) mRNA appeared to be derived from the previously characterized 8.4-kb transcript, while a 0.8-kb was splice product second 4.7-kb transcript that initiated 50 base pairs upstream J 1. interaction promoters with nuclear binding factors is also examined. potential role these transcripts in establishing rearrangement locus discussed.
Abstract Multiple myeloma is an incurable plasma cell malignancy for which existing animal models are limited. We have previously shown that the targeted expression of transgenes c-Myc and Bcl-XL in murine cells produces displays features human myeloma, such as localization tumor to bone marrow lytic lesions. isolated characterized vitro cultures adoptive transfers tumors from Bcl-xl/Myc transgenic mice. Tumors a plasmablastic morphology variable CD138, CD45, CD38, CD19. Spectral karyotyping...
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple and have increasingly demonstrated critical roles for tumor development relapse standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active MM. We tested efficacy of specific inhibitors large panel human MM cell lines (HMCLs) found only subset...
To further elucidate the potential role of mitogens and cytokines in regulation kappa immunoglobulin light-chain locus, we have characterized activation transcription factor binding, germ line transcription, DNase I hypersensitivity, Vκ-to-Jκ recombination upon induction model pre-B-cell lines. We find that both lipopolysaccharide (LPS) gamma interferon (IFN-γ) are capable activating locus. also transforming growth β is completely inhibiting LPS but has no apparent effect on including NF-κB....
Control of kappa immunoglobulin light-chain gene expression requires the interaction tissue specific and developmentally regulated DNA-binding proteins with enhancer.Deletion enhancer sequences upstream from NF-kB binding site has been shown to impair function, implying additional may interact these sequences.In surveying this region for sites protein binding, a novel DNA-protein interaction, designated kBF-A, was detected.The activity factor appears be activated pre-B cells correlates high...
Products of Ig kappa L chain gene rearrangement in a variety human B cell samples were investigated by sequential Southern blot hybridization analysis. By application four region-specific probes (C kappa, J U' and de) complete spectrum rearrangements, including both predicted novel products, detected. Nearly 30% the products detected reflect multiple recombination locus. The kappa-deleting element was responsible for 70% rearrangements that Interestingly, eight kappa-expressing exhibited...
Abstract Deregulation of the c-Myc oncogene is tightly associated with human and murine plasma cell (PC) neoplasms. Through analysis Ag-specific B responses in mice where Myc targeted to Igh Cα locus, we show here that dramatically impairs primary secondary Ab response. This impairment differentiation stage specific, since germinal center formation, affinity maturation, class switch recombination were intact. Examination PC viability revealed triggered apoptosis only upon final maturation...