Abstract:
:Lethal factor, the principal virulence factor of Bacillus anthracis, inhibits mitogen-activated protein kinase (MAPK) signaling by proteolytically cleaving MAPK kinases. Edema factor, another component of anthrax toxin, is an adenylate cyclase, which increases intracellular cAMP. Inhibition of MAPK signaling with either anthrax lethal toxin (LeTx) or small molecule MAPK kinase inhibitors triggers apoptosis in human melanoma cells. Normal melanocytes do not undergo apoptosis in response to MAPK inhibition but arrest in the G1 phase of the cell cycle. Importantly, in vivo treatment of human melanoma xenograft tumors in athymic nude mice with LeTx results in significant or complete tumor regression without apparent side effects, suggesting that inhibiting the MAPK signaling pathway may be a useful strategy for treating melanoma. Additionally, interrupting MAPK signaling with LeTx and elevating cAMP with anthrax edema toxin in both melanoma cells and melanocytes lead to dramatic melanin production, perhaps explaining the formation of blackened eschars in cutaneous anthrax.
journal_name
Proc Natl Acad Sci U S Aauthors
Koo HM,VanBrocklin M,McWilliams MJ,Leppla SH,Duesbery NS,Vande Woude GFdoi
10.1073/pnas.052707699keywords:
subject
Has Abstractpub_date
2002-03-05 00:00:00pages
3052-7issue
5eissn
0027-8424issn
1091-6490pii
052707699journal_volume
99pub_type
杂志文章abstract::Combined intracellular and microfluorometric recording techniques were used to evaluate whether the inhibition by cholinergic or adrenergic transmitters of the Ca2(+)-activated potassium current (IAHP) in hippocampal CA3 pyramidal cells was mediated by an alteration of depolarization-induced change in cytosolic free C...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.11.4083
更新日期:1990-06-01 00:00:00
abstract::The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a funct...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1500107112
更新日期:2015-06-09 00:00:00
abstract::In early brain development, ascending thalamocortical axons (TCAs) navigate through the ventral telencephalon (VTel) to reach their target regions in the young cerebral cortex. Descending, deep-layer cortical axons subsequently target appropriate thalamic and subcortical target regions. However, precisely how and when...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1324215111
更新日期:2014-02-11 00:00:00
abstract::Vanilloid receptor subunit 1 (VR1) appears to play a critical role in the transduction of noxious chemical and thermal stimuli by sensory nerve endings in peripheral tissues. Thus, VR1 antagonists are useful compounds to unravel the contribution of this receptor to pain perception, as well as to induce analgesia. We h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.022285899
更新日期:2002-02-19 00:00:00
abstract::By using a mixture of synthetic oligodeoxyribonucleotides as a probe, cloned cDNA sequences specific for low molecular weight (LMW) kininogen have been isolated from a cDNA library of bovine liver mRNA sequences. Nucleotide sequence analyses of cloned cDNA inserts have revealed that bovine liver LMW kininogens are enc...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.1.90
更新日期:1983-01-01 00:00:00
abstract::Pure water in a highly (1)H spin-polarized state is proposed as a contrast-agent-free contrast agent to visualize its macroscopic evolution in aqueous media by MRI. Remotely enhanced liquids for image contrast (RELIC) utilizes a (1)H signal of water that is enhanced outside the sample in continuous-flow mode and immed...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0610540104
更新日期:2007-02-06 00:00:00
abstract::Previous reports have shown that γδ T cells are important for the elimination of malaria parasites in humans and mice. However, how γδ T cells are involved in protective immunity against blood-stage malaria remains unknown. We infected γδ T-cell-deficient (TCRδ-KO) mice and control wild-type mice with Plasmodium bergh...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1204480109
更新日期:2012-07-24 00:00:00
abstract::We have explored the mechanism of genomic rearrangement in a hamster fibroblast cell culture system in which rearrangements are induced 5' to the endogenous thymidine kinase gene by chemical carcinogen treatment. The wild-type region around one rearrangement breakpoint was cloned and sequenced. With this sequence info...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.3.942
更新日期:1992-02-01 00:00:00
abstract::Abnormal H2O2 levels are closely related to many diseases, including inflammation and cancers. Herein, we simultaneously load HRP and its substrate, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), into liposomal nanoparticles, obtaining a Lipo@HRP&ABTS optical nanoprobe for in vivo H2O2-responsive chrom...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1701976114
更新日期:2017-05-23 00:00:00
abstract::One approach to understanding common human diseases is to determine the genetic defects responsible for similar diseases in animal models and place those defective genes in their corresponding biochemical pathways. Our laboratory is working with an animal model for human rheumatoid arthritis called collagen-induced ar...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.96.5.2210
更新日期:1999-03-02 00:00:00
abstract::Aspartate transcarbamoylase (EC 2.1.3.2) from Escherichia coli contains six zinc ions per molecule. Renaturation studies of this allosteric enzyme and its isolated subunits show that the metal binding site is in the regulatory polypeptide chain. Ultraviolet difference spectra of the cadmium and zinc derivatives have b...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.68.5.1019
更新日期:1971-05-01 00:00:00
abstract::Gene duplication is an important mechanism in the evolution of protein interaction networks. Duplications are followed by the gain and loss of interactions, rewiring the network at some unknown rate. Because rewiring is likely to change the distribution of network motifs within the duplicated interaction set, it shoul...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0707293105
更新日期:2008-01-22 00:00:00
abstract::Photo-triggered alpha-helix formation of a 16-residue peptide featuring a built-in conformational photoswitch is monitored by time-resolved IR spectroscopy. An experimental approach with 2-ps time resolution and a scanning range up to 30 micros is used to cover all time scales of the peptide dynamics. Experiments are ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0406948102
更新日期:2005-02-15 00:00:00
abstract::Nonribosomal peptides and polyketides are a diverse group of natural products with complex chemical structures and enormous pharmaceutical potential. They are synthesized on modular nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) enzyme complexes by a conserved thiotemplate mechanism. Here, we rep...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1401734111
更新日期:2014-06-24 00:00:00
abstract::In this paper, we report an example of the engineered expression of tetrameric β-galactosidase (β-gal) containing varying numbers of active monomers. Specifically, by combining wild-type and single-nucleotide polymorphism plasmids at varying ratios, tetrameric β-gal was expressed in vitro with one to four active monom...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1805690115
更新日期:2018-08-14 00:00:00
abstract::Erythropoietin regulates the proliferation and differentiation of erythroid precursor cells. Its effect is mediated by the erythropoietin receptor (EPOR), a member of a large family of cytokine receptors. The EPOR gene has recently been cloned, sequenced, and characterized. As shown experimentally, its intracellular C...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.10.4495
更新日期:1993-05-15 00:00:00
abstract::Methods are described for the removal of the sporophytic pollen grain coating of Brassica oleracea and for the isolation of coat polypeptides. The coat contains a small number of proteins ranging from 6 to 45 kDa. Many of the larger proteins are glycosylated, while all carry high positive charges resulting in pI value...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.90.2.467
更新日期:1993-01-15 00:00:00
abstract::A randomized double-blind controlled trial was conducted to determine the efficacy of passive immunotherapy in the treatment of symptomatic human immunodeficiency virus (HIV) infection. This trial included 86 symptomatic patients randomized to receive plasma rich in anti-HIV-1 antibody or standard seronegative plasma....
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1073/pnas.92.4.1195
更新日期:1995-02-14 00:00:00
abstract::The precise determination of de novo genetic variants has enormous implications across different fields of biology and medicine, particularly personalized medicine. Currently, de novo variations are identified by mapping sample reads from a parent-offspring trio to a reference genome, allowing for a certain degree of ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1802244115
更新日期:2018-05-22 00:00:00
abstract::When an unusually high frequency of an allele is encountered in a population, "founder effect" is often invoked as an explanation. As usually used, the term implies the disproportionate increase through chance (rather than selection) of an allele contributed to the population by a particular ancestor. While genetic th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.75.3.1442
更新日期:1978-03-01 00:00:00
abstract::In addition to guiding proteins to defined genomic loci, DNA can act as an allosteric ligand that influences protein structure and activity. Here we compared genome-wide binding, transcriptional regulation, and, using NMR, the conformation of two glucocorticoid receptor (GR) isoforms that differ by a single amino acid...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1316235110
更新日期:2013-10-29 00:00:00
abstract::Genetic and biochemical studies on enzymes known to be involved in regulating DNA supercoiling yield a complex spectrum of effects on the Escherichia coli SOS system. Previous studies indicated that only inhibition of DNA gyrase by antibiotics that act on the DNA gyrase A subunit results in turning on the E. coli SOS ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.9.2510
更新日期:1983-05-01 00:00:00
abstract::An effective vaccine that can protect against HIV infection does not exist. A major reason why a vaccine is not available is the high mutability of the virus, which enables it to evolve mutations that can evade human immune responses. This challenge is exacerbated by the ability of the virus to evolve compensatory mut...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.2022496118
更新日期:2021-02-02 00:00:00
abstract::Meiotic recombination in the yeast Saccharomyces cerevisiae is initiated by programmed double-strand breaks at selected sites throughout the genome (hotspots). alpha-Hotspots are binding sites for transcription factors. Double-strand breaks at alpha-hotspots require binding of transcription factor but not high levels ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.201529598
更新日期:2001-12-04 00:00:00
abstract::Formulas are derived for the effect of size on a free-swimming microbe's ability to follow chemical, light, or temperature stimuli or to disperse in random directions. The four main assumptions are as follows: (i) the organisms can be modeled as spheres, (ii) the power available to the organism for swimming is proport...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.94.20.10949
更新日期:1997-09-30 00:00:00
abstract::Individuals with developmental dyslexia vary in their ability to improve reading skills, but the brain basis for improvement remains largely unknown. We performed a prospective, longitudinal study over 2.5 y in children with dyslexia (n = 25) or without dyslexia (n = 20) to discover whether initial behavioral or brain...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1008950108
更新日期:2011-01-04 00:00:00
abstract::Utilization of transcription factors might be a powerful approach to modification of metabolism for a generation of crops having superior characteristics because a single transcription factor frequently regulates coordinated expression of a set of key genes for respective pathways. Here, we apply the plant-specific Do...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402267101
更新日期:2004-05-18 00:00:00
abstract::We recently showed that the mammalian genome encodes >1,000 large intergenic noncoding (linc)RNAs that are clearly conserved across mammals and, thus, functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes, including cell-cycle regulation, immune surveillance, and embryonic...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0904715106
更新日期:2009-07-14 00:00:00
abstract::Genetic switches based on the [Formula: see text] system are master regulators of an array of cellular responses. Recent kinetic experiments have shown that [Formula: see text] can actively remove NF-κB bound to its genetic sites via a process called "molecular stripping." This allows the [Formula: see text] switch to...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1520483112
更新日期:2016-01-05 00:00:00
abstract::During tRNA biosynthesis the 5'-leader sequences in precursor tRNAs are removed by the ribonucleoprotein RNase P, an enzyme whose RNA moiety is required for activity. To clarify some aspects of the enzyme mechanism, we examined substrate binding and product formation with mutant precursor tRNAs. Mutations G-1----A or ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.5.1379
更新日期:1988-03-01 00:00:00