Abstract:
:An essential step in the pathogenesis of human papillomavirus (HPV)-associated cancers is the dysregulated expression of the viral oncogenes. The papillomavirus E2 protein can silence the long control region (LCR) promoter that controls viral E6 and E7 oncogene expression. The mechanisms by which E2 represses oncogene expression and the cellular factors through which E2 mediates this silencing are largely unknown. We conducted an unbiased, genome-wide siRNA screen and series of secondary screens that identified 96 cellular genes that contribute to the repression of the HPV LCR. In addition to confirming a role for the E2-binding bromodomain protein Brd4 in E2-mediated silencing, we identified a number of genes that have not previously been implicated in E2 repression, including the demethylase JARID1C/SMCX as well as EP400, a component of the NuA4/TIP60 histone acetyltransferase complex. Each of these genes contributes independently and additively to E2-mediated silencing, indicating that E2 functions through several distinct cellular complexes to repress E6 and E7 expression.
journal_name
Proc Natl Acad Sci U S Aauthors
Smith JA,White EA,Sowa ME,Powell ML,Ottinger M,Harper JW,Howley PMdoi
10.1073/pnas.0914818107subject
Has Abstractpub_date
2010-02-23 00:00:00pages
3752-7issue
8eissn
0027-8424issn
1091-6490pii
0914818107journal_volume
107pub_type
杂志文章abstract::Cyclin E is an important regulator of cell cycle progression that together with cyclin-dependent kinase (cdk) 2 is crucial for the G1/S transition during the mammalian cell cycle. Previously, we showed that severe overexpression of cyclin E protein in tumor cells and tissues results in the appearance of lower molecula...
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.93.26.15215
更新日期:1996-12-24 00:00:00
abstract::Invariant natural killer T cell (NKT) cells (iNKT cells) produce both T-helper 1 (Th1) and T-helper 2 cytokines in response to α-Galactosylceramide (α-GalCer) stimulation and are thought to be the important effectors in the regulation of both innate and adaptive immunity involved in autoimmune disorders, microbial inf...
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.1114255108
更新日期:2011-10-18 00:00:00
abstract::The pyridoxal 5'-phosphate cofactor of glycogen phosphorylase a (1,4-alpha-D-glucan:orthophosphate alpha-glucosyltransferase, EC2.4.1.1.) has been positioned on the protomer with x-ray diffraction data, chemical markers, and sequence information. The electron density was computed from 3.0-A resolution phases calculate...
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.74.11.4757
更新日期:1977-11-01 00:00:00
abstract::Relatively little is understood about the dynamics of global host-pathogen transcriptome changes that occur during bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS) infection of the oropharynx provokes a distinct host transcriptome response, we performed genome-wide trans...
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.0906384107
更新日期:2010-03-09 00:00:00
abstract::Oxidants, such as those generated by metabolically activated phagocytes in inflammation, have been implicated in the metabolic activation of carcinogens, and in this study we demonstrate that the interaction of (+/-)-trans-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene (BP 7,8-dihydrodiol) with phorbol ester-stimulated polym...
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.82.15.5194
更新日期:1985-08-01 00:00:00
abstract::The probability of choosing an alternative in a long sequence of repeated choices is proportional to the total reward derived from that alternative, a phenomenon known as Herrnstein's matching law. This behavior is remarkably conserved across species and experimental conditions, but its underlying neural mechanisms st...
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.0505220103
更新日期:2006-10-10 00:00:00
abstract::Satellite tobacco necrosis virus (STNV) is one of the smallest viruses known. Its genome encodes only its coat protein (CP) subunit, relying on the polymerase of its helper virus TNV for replication. The genome has been shown to contain a cryptic set of dispersed assembly signals in the form of stem-loops that each pr...
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.1706951114
更新日期:2017-11-14 00:00:00
abstract::The human immunodeficiency virus 1 (HIV-1) Tat protein suppresses antigen-induced, but not mitogen-induced, activation of human T cells when added to T-cell cultures [Viscidi, R. P., Mayur, K., Lederman, H. M. & Frankel, A. D. (1989) Science 246, 1606-1608]. This activity is potentially pertinent to the development 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.91.14.6594
更新日期:1994-07-05 00:00:00
abstract::Invariant natural killer T (iNKT) cells recognize self lipid antigens presented by CD1d molecules. The nature of the self-antigens involved in the development and maturation of iNKT cells is poorly defined. Lysophospholipids are self-antigens presented by CD1d that are generated through the action of phospholipases A1...
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.1302923110
更新日期:2013-03-26 00:00:00
abstract::Fungi of the recently defined order Sebacinales (Basidiomycota) are involved in a wide spectrum of mutualistic symbioses (including mycorrhizae) with various plants, thereby exhibiting a unique potential for biocontrol strategies. The axenically cultivable root endophyte Piriformospora indica is a model organism of 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.0605697103
更新日期:2006-12-05 00:00:00
abstract::One of the most fundamental functions of the brain is to predict upcoming events on the basis of the recent past. A closely related function is to signal when a prediction has been violated. The identity of the brain regions that mediate these functions is not known. We set out to determine whether they are implemente...
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.1112895108
更新日期:2011-11-29 00:00:00
abstract::O(6)-methylguanine (O(6)meG) and related modifications of guanine in double-stranded DNA are functionally severe lesions that can be produced by many alkylating agents, including N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a potent carcinogen. O(6)meG is repaired through its demethylation by the O(6)-alkylguanine-DNA...
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.0812316106
更新日期:2009-02-17 00:00:00
abstract::During response of budding yeast to peptide mating pheromone, the cell becomes markedly polarized and MAPK scaffold protein Ste5 localizes to the resulting projection (shmoo tip). We demonstrated before that this recruitment is essential for sustained MAPK signaling and requires interaction of a pleckstrin homology (P...
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.1005817107
更新日期:2010-06-29 00:00:00
abstract::The kinase Cdc2p is a central regulator of entry into and progression through nuclear division during mitosis and meiosis in eukaryotes. Cdc2p is activated at the onset of mitosis by dephosphorylation on tyrosine-15, the phosphorylation status of which is determined mainly by the kinase Wee1p and the phosphatase Cdc25...
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.0702906104
更新日期:2007-09-11 00:00:00
abstract::In choanoflagellates, the closest living relatives of animals, multicellular rosette development is regulated by environmental bacteria. The simplicity of this evolutionarily relevant interaction provides an opportunity to identify the molecules and regulatory logic underpinning bacterial regulation of development. We...
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.1605015113
更新日期:2016-07-12 00:00:00
abstract::Transcript accumulation and translation of psbA as well as processing of the D1 precursor protein were investigated in relation to chlorophyll availability in vivo in cyanobacterial strains lacking photosystem I (PS I). The psbA transcript level was almost independent of chlorophyll availability and was approximately ...
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.95.10.5830
更新日期:1998-05-12 00:00:00
abstract::We previously found that a minor fraction of single-stranded DNA (ss-DNA) isolated from native nuclear DNA of normal chicken embryonic cells and cells of other species hybridized with bulk nuclear DNA or cellular RNA in great excess. At least one-third of ss-DNA belonging to the nonrepetitious part of the cell genome ...
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.74.9.3720
更新日期:1977-09-01 00:00:00
abstract::Old noninbred fly mortality decreases according to the inverse linear law and reduces to a single suborder-specific age. Relative child mortality (the mortality at a given age related to the mortality at 10 years) from 1 mo to 11 years is the same with 8% mean accuracy for all humans, independent of race, country, sex...
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.95.15.9037
更新日期:1998-07-21 00:00:00
abstract::It is possible, by using Fourier-transform infrared (FTIR) difference spectroscopy, to detect the conformational changes occurring in both the protein and the chromophore of bacteriorhodopsin during the photocycle. In contrast to Raman spectroscopy, a laser is unnecessary and hence the problem of a perturbing probe be...
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.79.13.4045
更新日期:1982-07-01 00:00:00
abstract::The dilute (d) coat color mutation on chromosome 9 is closely associated with an ecotropic murine leukemia virus (MuLV) genome [Jenkins, N.A., Copeland, N.G., Taylor, B.A. & Lee, B.K. (1981) Nature 293, 370-374]. DBA/2J mice homozygous for the reverse mutation to wild type at the dilute locus (d+2J) lack ecotropic vir...
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.80.1.247
更新日期:1983-01-01 00:00:00
abstract::The transformation of new experiences into lasting memories is thought to be mediated by postencoding reactivation or the reexpression of activity patterns that characterize prior encoding experiences during subsequent offline periods. Although hippocampal reactivation has been well-described in the rodent, evidence f...
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.1308499110
更新日期:2013-11-26 00:00:00
abstract::As assessed by ultrastructure, histochemical staining, and T-cell dependency, in vitro-differentiated inter-leukin 3-dependent mouse mast cells are comparable to the mast cells that reside in the gastrointestinal mucosa but not in the skin or the serosal cavity of the mouse. We now demonstrate that when cloned interle...
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.85.2.569
更新日期:1988-01-01 00:00:00
abstract::The subdivision of all the experimental days of the Whitetop project into two approximately equal groups, group W with predominantly westerly winds aloft and group E with frequent easterly winds, shows a remarkable difference in the apparent effect of seeding. On W days there was no detectable effect of seeding on rai...
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.64.3.810
更新日期:1969-11-01 00:00:00
abstract::The only major glutamate receptor membrane-associated guanylate kinase scaffolds expressed in the young superficial superior colliculus (SC) are synapse-associated protein 102 (SAP102) and postsynaptic density protein 95 (PSD95). In this, as in all visual brain regions examined, synaptic PSD95 increases rapidly follow...
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.1215854110
更新日期:2013-01-08 00:00:00
abstract::Infected-cell protein 4 (ICP4), the major regulatory protein specified by herpes simplex virus 1 in infected cells, binds to homologs of the sequence ATCGTCnnnnYCGRC (A sites, where n is any nucleotide, Y is a pyrimidine, and R is a purine) and to unrelated sequences for which no consensus sequence has been derived (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.86.24.9808
更新日期:1989-12-01 00:00:00
abstract::Deuterium Fourier-transform nuclear magnetic resonance spectra have been obtained of 1-myristoyl 2-(14,14,14-trideutero)myristoyl phosphatidylcholine bilayers at 34.1 MHz by using the quadrupole echo pulse technique. Thereby, we have investigated the effects upon the deuterated dimyristoyl phosphatidylcholine bilayers...
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.75.10.4657
更新日期:1978-10-01 00:00:00
abstract::The three-dimensional structures of avian H5 and swine H9 influenza hemagglutinins (HAs) from viruses closely related to those that caused outbreaks of human disease in Hong Kong in 1997 and 1999 were determined bound to avian and human cell receptor analogs. Emerging influenza pandemics have been accompanied by the e...
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.201401198
更新日期:2001-09-25 00:00:00
abstract::Historical scenarios of evolution of avian plumage coloration have been called into question with the discoveries that most birds can see UV light (which normal humans cannot), and that UV-reflecting plumages are widespread in birds. Several examples of sexual dichromatism not detectable with human visual capabilities...
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.0501891102
更新日期:2005-08-02 00:00:00
abstract::Cerebellar granule cells are the most abundant neurons in the brain, and granule cell precursors (GCPs) are a common target of transformation in the pediatric brain tumor medulloblastoma. Proliferation of GCPs is regulated by the secreted signaling molecule Sonic hedgehog (Shh), but the mechanisms by which Shh control...
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.0832317100
更新日期:2003-06-10 00:00:00
abstract::Predominant usage of V beta 8.2 gene segments, encoding a T-cell receptor (TCR) beta chain variable region, has been reported for pathogenic Lewis rat T cells reactive to myelin basic protein (MBP). However, up to 75% of the alpha/beta T cells in a panel of MBP-specific T-cell lines did not display TCR V beta 8.2, V 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.92.13.5850
更新日期:1995-06-20 00:00:00