- DNA Repair Mechanisms
- DNA and Nucleic Acid Chemistry
- Advanced Proteomics Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Cancer-related Molecular Pathways
- Carcinogens and Genotoxicity Assessment
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Alzheimer's disease research and treatments
- Metabolomics and Mass Spectrometry Studies
- Peptidase Inhibition and Analysis
- RNA Interference and Gene Delivery
- HIV Research and Treatment
- Bacterial Genetics and Biotechnology
- HIV/AIDS drug development and treatment
- Molecular Biology Techniques and Applications
- CAR-T cell therapy research
- Advanced biosensing and bioanalysis techniques
- Glycosylation and Glycoproteins Research
- Polyomavirus and related diseases
- Animal Genetics and Reproduction
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Bacteriophages and microbial interactions
- Biochemical and Molecular Research
Amunix (United States)
2012-2023
Sunesis (United States)
2023
Sanofi (United States)
2023
Sanofi (Mexico)
2022
National Institutes of Health
2013
Cipher Gene (China)
2007
Biomark (United States)
2007
Vanderbilt University
1997-2004
Vanderbilt-Ingram Cancer Center
2002-2004
University of Rochester
2004
Regulation of NF-kappaB occurs through phosphorylation-dependent ubiquitination IkappaBalpha, which is degraded by the 26S proteasome. Recent studies have shown that IkappaBalpha carried out a ubiquitin-ligase enzyme complex called SCF(beta(TrCP)). Here we show Nedd8 modification Cul-1 component SCF(beta(TrCP)) important for function in IkappaBalpha. In cells, Nedd8-conjugated was complexed with two substrates SCF(beta(TrCP)), phosphorylated and beta-catenin, indicating Nedd8-Cul-1...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleotide Excision Repair DNA Synthesis by Polymerase .epsilon. in the Presence of PCNA, RFC, and RPAMahmud K. Shivji, Vladimir N. Podust, Ulrich Huebscher, Richard D. WoodCite this: Biochemistry 1995, 34, 15, 5011–5017Publication Date (Print):April 18, 1995Publication History Published online1 May 2002Published inissue 18 April 1995https://pubs.acs.org/doi/10.1021/bi00015a012https://doi.org/10.1021/bi00015a012research-articleACS...
Temporal control of p27 Kip1 (p27) degradation imposes periodicity in its activity during cell cycle progression and accumulation exit. Degradation is initiated by phosphorylation at Thr-187, which marks the protein for ubiquitination SCF Skp2 subsequent proteolysis 26S proteasome. Here we show that extracts depends on presence ubiquitin-like Nedd8 enzymes catalyze conjugation to proteins. Moreover, reconstitution recombinant also requires pathway components. Inactivation a dominant negative...
Discovery of the central role hepcidin in body iron regulation has shed new light on pathophysiology disorders. Information is lacking newer analytical approaches to measure serum and urine. Recent reports measurement urine by surface-enhanced laser-desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) necessitate clinical evaluation MS-based methodologies.We used SELDI-TOF MS, immunocapture, tandem MS identify characterize In addition diagnostic application, we investigated...
Protein and peptides in tears play an important role ocular surface diseases. In previous studies, changes have been demonstrated the electrophoretic protein profiles of patients with dry eye. The purpose this work was to determine usefulness surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) ProteinChip Array (Ciphergen Biosystems, Inc., Fremont, CA) technology for automated analysis proteins tear fluid.Patients eye (DRY, n = 88) healthy subjects...
High-throughput proteomic methods for disease biomarker discovery in human serum are promising, but concerns exist regarding reproducibility of results and variability introduced by sample handling. This study investigated the influence different preanalytic handling on surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) protein profiles prefractionated serum. We whether older collections with longer transit times yield useful profiles, sought to...
To enhance the therapeutic index of T-cell engagers (TCEs), we engineered masked, precision-activated TCEs (XPAT proteins), targeting a tumor antigen (human epidermal growth factor receptor 2 (HER2) or (EGFR)) and CD3. Unstructured XTEN polypeptide masks flank N C termini TCE are designed to be released by proteases in microenvironment. In vitro, unmasked HER2-XPAT (uTCE) demonstrates potent cytotoxicity, with masking providing up 4-log-fold protection. vivo, protein induces...
<h3>Objective</h3> To use proteomic analysis of cerebrospinal fluid to discover novel proteins and peptides able differentiate between patients with stable mild cognitive impairment (MCI) those who will progress Alzheimer disease (AD). <h3>Design</h3> Baseline samples from MCI healthy controls were profiled using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. <h3>Setting</h3> Memory disorder clinic. <h3>Participants</h3> Patients (n = 113), whom 56 cognitively...
We have purified a high molecular weight complex (RC-1) from calf thymus nuclei that catalyzes recombinational repair of double-strand gaps and deletions in DNA by gene conversion as well cross-over events leading to cointegrant products. These been detected polymerase chain reaction analysis using oligonucleotide primer pairs detect joined sequences originally present on only one or the other recombination substrates. RC-1 has an apparent mass about 550-600 kDa contains at least five...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMechanism of Inhibition Proliferating Cell Nuclear Antigen-Dependent DNA Synthesis by the Cyclin-Dependent Kinase Inhibitor p21Vladimir N. Podust, Larissa M. Francoise Goubin, Bernard Ducommun, and Ulrich HuebscherCite this: Biochemistry 1995, 34, 27, 8869–8875Publication Date (Print):July 11, 1995Publication History Published online1 May 2002Published inissue 11 July...
Globally, heterosexual intercourse is the primary route of HIV-1 (HIV) transmission. It follows that mechanisms protect against HIV infection are likely operative at genital mucosa. In HIV-resistant Kenyan sex workers who highly exposed to yet remain uninfected, protection correlates with HIV-specific immune responses and genetic factors. However, these factors do not entirely explain this model natural immunity HIV. We hypothesized may be mediated by innate proteins in tract workers.The...
The antibody-drug conjugate (ADC) is a well-validated modality for the cell-specific delivery of small molecules with impact expanding rapidly beyond their originally-intended purpose treating cancer. However, antibody-mediated (AMD) remains inefficient, limiting its applicability to targeting highly potent payloads cells high antigen expression. Maximizing number delivered per antibody one key way in which efficiency can be improved, although this has been challenging carry out; few...
The ability of DNA polymerases (pols) to catalyze the template-directed synthesis duplex oligonucleotides containing a nonstandard Watson-Crick base pair between nucleotide bearing 5-(2,4-diaminopyrimidine) heterocycle (d kappa) and either deoxyxanthosine (dX) or N1-methyloxoformycin B (pi) has been investigated. kappa-X kappa-pi pairs are jointed by hydrogen bonding pattern different from exclusive those joining AT GC pairs. Reverse transcriptase human immunodeficiency virus type 1 (HIV-1)...
Eukaryotic DNA polymerase δ is thought to consist of three (budding yeast) or four subunits (fission yeast, mammals). Four human genes encoding polypeptides p125, p50, p66, and p12 have been assigned as δ. However, rigorous purification bovine from natural sources has usually yielded two-subunit preparations containing only p125 p50 polypeptides. To reconstitute an intact δ, we constructed recombinant baculoviruses the subunits. From insect cells infected with baculoviruses, protein expected...
We have examined the capacity of calf thymus DNA polymerases alpha, beta, delta, and epsilon to perform in vitro translesion synthesis on a substrate containing single d(GpG)-cisplatin adduct placed codon 13 human HRAS gene. found that catalyzed by was blocked at base preceding lesion. Addition proliferating cell nuclear antigen polymerase delta replication protein A alpha did not restore their elongate past adduct. On other hand, beta efficiently bypassed cisplatin Furthermore, we observed...
Replication protein A (RP-A) is a heterotrimeric complex conserved in eukaryotic cells. It binds to single-stranded DNA and essential for initiation elongation of replication. In this communication we give evidence that can unwind independent magnesium ATP, two cofactors bona fide helicase activity. RP-A up at least 350 basepairs appears be required stoichiometric amounts. The reaction extremely sensitive NaCl MgCl2. This activity RF-A suggestive possible unwinding function replication eukaryotes.
The toroidal damage checkpoint complex Rad9–Rad1–Hus1 (9-1-1) has been characterized as a sensor of DNA damage. Flap endonuclease 1 (FEN1) is structure-specific nuclease involved both in removing initiator RNA from Okazaki fragments and repair pathways. FEN1 activity stimulated by proliferating cell nuclear antigen (PCNA), sliding clamp that acts platform for replication complexes. We show 9-1-1 also binds stimulates FEN1. Stimulation observed on variety flap, nick, gapped substrates...
To understand the mechanism of action two eukaryotic replication auxiliary proteins proliferating cell nuclear antigen (PCNA) and factor C (RF-C), we constructed a plasmid for producing PCNA which could be 32P labelled in vitro. This allowed us to analyze assembly directly on DNA examine this process absence synthesis. By using closed circular double-stranded or gapped protein-DNA complex formation, following results were obtained, (i) RF-C can load an ATP-dependent manner DNA, no 3'-OH ends...