Abstract:
:The E6 protein of the high-risk human papillomaviruses inactivates the tumor suppressor protein p53 by stimulating its ubiquitinylation and subsequent degradation. Ubiquitinylation is a multistep process involving a ubiquitin-activating enzyme, one of many distinct ubiquitin-conjugating enzymes, and in certain cases, a ubiquitin ligase. In human papillomavirus-infected cells, E6 and the E6-associated protein are thought to act as a ubiquitin-protein ligase in the ubiquitinylation of p53. Here we describe the cloning of a human ubiquitin-conjugating enzyme that specifically ubiquitinylates E6-associated protein. Furthermore, we define the biochemical pathway of p53 ubiquitinylation and demonstrate that in vivo inhibition of various components in the pathway leads to an inhibition of E6-stimulated p53 degradation.
journal_name
Proc Natl Acad Sci U S Aauthors
Rolfe M,Beer-Romero P,Glass S,Eckstein J,Berdo I,Theodoras A,Pagano M,Draetta Gdoi
10.1073/pnas.92.8.3264subject
Has Abstractpub_date
1995-04-11 00:00:00pages
3264-8issue
8eissn
0027-8424issn
1091-6490journal_volume
92pub_type
杂志文章abstract::Methylmalonyl-CoA mutase (EC 5.4.99.2) is a mitochondrial matrix enzyme whose activity is deficient in the inherited disorder methylmalonic acidemia. Previous studies on primary fibroblast cell lines from patients with methylmalonic acidemia have delineated a variety of biochemical phenotypes underlying this disorder....
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.87.8.3147
更新日期:1990-04-01 00:00:00
abstract::Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a ravaging condition of progressive lung scarring and destruction. Anti-inflammatory therapies including corticosteroids have limited efficacy in this ultimately fatal disorder. An important unmet need is to identify new agents that interact with key ...
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.1001520107
更新日期:2010-08-10 00:00:00
abstract::Molecular beacons are DNA probes that form a stem-and-loop structure and possess an internally quenched fluorophore. When they bind to complementary nucleic acids, they undergo a conformational transition that switches on their fluorescence. These probes recognize their targets with higher specificity than probes that...
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.96.11.6171
更新日期:1999-05-25 00:00:00
abstract::Retinitis pigmentosa (RP) is an inherited neurodegenerative disease, in which the death of mutant rod photoreceptors leads secondarily to the non-cell autonomous death of cone photoreceptors. Gene therapy is a promising treatment strategy. Unfortunately, current methods of gene delivery treat only a fraction of diseas...
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.1615394114
更新日期:2017-05-16 00:00:00
abstract::Skeletal muscle adapts to different patterns of motor nerve activity by alterations in gene expression that match specialized properties of contraction, metabolism, and muscle mass to changing work demands (muscle plasticity). Calcineurin, a calcium/calmodulin-dependent, serine-threonine protein phosphatase, has been ...
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.0308179101
更新日期:2004-06-22 00:00:00
abstract::This paper explores the explanations for, and consequences of, the early appearance of food production outside the Fertile Crescent of Southwest Asia, where it originated in the 10th/9th millennia cal BC. We present evidence that cultivation appeared in Central Anatolia through adoption by indigenous foragers in the m...
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.1800163115
更新日期:2018-04-03 00:00:00
abstract::An extracellular patch electrode was used to record ionic currents from individual complement-induced channels in the membranes of antibody-coated skeletal muscle. The amplitude of the single-channel currents leads to an estimate of 90 pS for the unit conductance. The kinetics of channel opening and closing show marke...
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.78.10.6421
更新日期:1981-10-01 00:00:00
abstract::The decrease with age of the adrenal-secreted dehydroepiandrosterone sulfate (DHEAS) in serum has suggested that it may be causally related to longevity. For the PAQUID [People (Personnes) Aged (Agées) About What (Quid, in Latin)] cohort of elderly subjects, we have previously reported higher DHEAS in men than in wome...
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.121177998
更新日期:2001-07-03 00:00:00
abstract::Refinement of neural circuits in the mammalian cerebral cortex shapes brain function during development and in the adult. However, the signaling mechanisms underlying the synapse-specific shrinkage and loss of spiny synapses when neural circuits are remodeled remain poorly defined. Here, we show that low-frequency glu...
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.1214705110
更新日期:2013-01-22 00:00:00
abstract::We investigated the structural and functional alterations of active lamellae during initial cell-cell collision and establishment of cell-cell contacts in wounded cultures of nontransformed rat epitheliocytes (IAR-2 line) and their ras-transformed descendants (C4 line). Typically, the leading edges of nontransformed 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.94.3.879
更新日期:1997-02-04 00:00:00
abstract::Synthetic bradykinin, a nonapeptide formed from alpha-2 globulin in plasma, injected intra-arterially or intraperitoneally in cats in doses of 10-50 mug, evoked activity in the central nervous system in pathways associated with the signaling of pain. Similar injections of bradykinin in intact normal cats and dogs evok...
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.63.3.705
更新日期:1969-07-01 00:00:00
abstract::Polymorphism in materials often leads to significantly different physical properties--the rutile and anatase polymorphs of TiO2 are a prime example. Polytypism is a special type of polymorphism, occurring in layered materials when the geometry of a repeating structural layer is maintained but the layer-stacking sequen...
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.1502460112
更新日期:2015-03-17 00:00:00
abstract::Effects of opiate receptor antagonists on centrally mediated cardiovascular responses to clonidine and beta-endorphin were studied in urethane-anesthetized spontaneously hypertensive Okamoto-Aoki rats (SHR), normotensive Sprague-Dawley rats, and Sprague-Dawley rats made hypertensive with deoxycorticosterone pivalate/s...
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.84.23.8637
更新日期:1987-12-01 00:00:00
abstract::The cellulose synthesizing terminal complex consisting of subunits A, B, C, and D in Acetobacter xylinum spans the outer and inner cell membranes to synthesize and extrude glucan chains, which are assembled into subelementary fibrils and further into a ribbon. We determined the structures of subunit D (AxCeSD/AxBcsD) ...
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.1000601107
更新日期:2010-10-19 00:00:00
abstract::Surface proteins of mouse thymus and spleen cells were radioiodinated with lactoperoxidase. After solubilization, the labeled proteins were precipitated by antibodies directed against mouse immunoglobulin chains; the precipitates were analyzed by radioautography after Na dodecyl sulfate-gel electrophoresis. Radioactiv...
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.70.10.2879
更新日期:1973-10-01 00:00:00
abstract::Mature immunologically competent dendritic cells are the most efficient antigen-presenting cells that powerfully activate T cells and initiate and sustain immune responses. Indeed, dendritic cells are able to efficiently capture antigens, express high levels of costimulatory molecules, and produce the combination of 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.190204697
更新日期:2000-09-26 00:00:00
abstract::A mutant strain deficient in RNase T was isolated and used to study the role of this enzyme in Escherichia coli. Strains lacking as much as 70% of RNase T activity, alone or in combination with the absence of other RNases, display normal growth properties. However, in cca strains, which lack tRNA nucleotidyltransferas...
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.82.19.6427
更新日期:1985-10-01 00:00:00
abstract::Diffuse celestial sources of relatively low surface brightness such as the Milky Way, zodiacal light, and gegenschein (or contre lumière) can be studied most reliably from above the earth's atmosphere with equipment flown in artificial satellites. We review the techniques used and some of the difficulties encountered ...
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.69.3.694
更新日期:1972-03-01 00:00:00
abstract::The Ritz upper bound to eigenvalues of Hermitian operators is essential for many applications in science. It is a staple of quantum chemistry and physics computations. The lower bound devised by Temple in 1928 [G. Temple, Proc. R. Soc. A Math. Phys. Eng. Sci. 119, 276-293 (1928)] is not, since it converges too slowly....
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.2007093117
更新日期:2020-07-14 00:00:00
abstract::We propose a motility mechanism that may result in the displacement of objects within the cell. The mechanism, which we call polymer-guided diffusion, involves a microscopic cycle of polymer association and dissociation from a lateral binding site. Reassociation occurs at the polymer subunit adjacent to that which has...
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.84.11.3599
更新日期:1987-06-01 00:00:00
abstract::Genetic data in the mouse have shown that endothelin 3 (ET3) and its receptor B (ETRB) are essential for the development of two neural crest (NC) derivatives, the melanocytes and the enteric nervous system. We report here the effects of ET3 in vitro on the differentiation of quail trunk NC cells (NCC) in mass and clon...
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.95.24.14214
更新日期:1998-11-24 00:00:00
abstract::We have isolated RNA ligands with low-nanomolar affinity and high specificity to basic fibroblast growth factor from a pool of 10(14) molecules containing 30 randomized positions by the systematic evolution of ligands by exponential enrichment (SELEX) procedure. High-affinity ligands could be classified into two famil...
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.90.23.11227
更新日期:1993-12-01 00:00:00
abstract::A fundamental aspect of climate change is the potential shifts in flowering phenology and pollen initiation associated with milder winters and warmer seasonal air temperature. Earlier floral anthesis has been suggested, in turn, to have a role in human disease by increasing time of exposure to pollen that causes aller...
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.1014107108
更新日期:2011-03-08 00:00:00
abstract::Legionella pneumophila is an intracellular parasite of freshwater protozoa and human macrophages. Recent studies determined that the macrophage infectivity potentiator (Mip) surface protein, a prokaryotic homolog of the FK506-binding proteins, is required for optimal infection of macrophages. To determine whether Mip ...
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.89.11.5188
更新日期:1992-06-01 00:00:00
abstract::Expression of the two X-linked loci glucose-6-phosphate dehydrogenase (G6PD; EC 1.1.1.49) and hypoxanthine:guanine phosphoribosyltransferase (HGPRT; EC 2.4.2.8) was studied in single hair follicles of two females who were heterozygous for both of these genes (double heterozygotes). The coupling phase for these two loc...
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.68.7.1425
更新日期:1971-07-01 00:00:00
abstract::A strong mutator effect has been observed in Escherichia coli K-12 strains mutated in the bglY gene (27 min). The frequency of point mutations is not modified in bglY mutant strains. In contrast, a strong increase in spontaneous generation of large deletions has been observed in these strains, both for chromosomal mar...
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.87.1.360
更新日期:1990-01-01 00:00:00
abstract::The substrate specificity of thermophilic xylose isomerase from Clostridium thermosulfurogenes was examined by using predictions from the known crystal structure of the Arthrobacter enzyme and site-directed mutagenesis of the thermophile xylA gene. The orientation of glucose as a substrate in the active site of the 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.88.9.4015
更新日期:1991-05-01 00:00:00
abstract::During organogenesis, the final size of mature cell populations depends on their rates of differentiation and expansion. Because transient expression of Neurogenin3 (Neurog3) in progenitor cells in the developing pancreas initiates their differentiation to mature islet cells, we examined the role of Neurog3 in cell cy...
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.1004842108
更新日期:2011-01-04 00:00:00
abstract::A library of Photobacterium phosphoreum DNA was screened in lambda 2001 for the lumazine protein gene, using two degenerate 17-mer oligonucleotide probes that were deduced from a partial protein primary sequence. The lumazine protein gene was localized to a 3.4-kilobase BamHI/EcoRI fragment in one clone. The fragment ...
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.88.4.1100
更新日期:1991-02-15 00:00:00
abstract::IL-17 is a T cell-derived, proinflammatory cytokine that is suspected to be involved in the development of various inflammatory diseases. Although there are elevated levels of IL-17 in synovial fluid of patients with rheumatoid arthritis, the pathogenic role of IL-17 in the development of rheumatoid arthritis remains ...
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.1035999100
更新日期:2003-05-13 00:00:00