Abstract:
:Diffuse large B cell lymphomas (DLBCLs) often express BCL6, a transcriptional repressor required for the formation of normal germinal centers. In a subset of DLBCLs, BCL6 is deregulated by chromosomal translocations or aberrant somatic hypermutation; in other tumors, BCL6 expression may simply reflect germinal center lineage. DLBCLs dependent on BCL6-regulated pathways should exhibit differential regulation of BCL6 target genes. Genomic array ChIP-on-chip was used to identify the cohort of direct BCL6 target genes. This set of genes was enriched in modulators of transcription, chromatin structure, protein ubiquitylation, cell cycle, and DNA damage responses. In primary DLBCLs classified on the basis of gene expression profiles, these BCL6 target genes were clearly differentially regulated in "BCR" tumors, a subset of DLBCLs with increased BCL6 expression and more frequent BCL6 translocations. In a panel of DLBCL cell lines analyzed by expression arrays and classified according to their gene expression profiles, only BCR tumors were highly sensitive to the BCL6 peptide inhibitor, BPI. These studies identify a discrete subset of DLBCLs that are reliant on BCL6 signaling and uniquely sensitive to BCL6 inhibitors. More broadly, these data show how genome-wide identification of direct target genes can identify tumors dependent on oncogenic transcription factors and amenable to targeted therapeutics.
journal_name
Proc Natl Acad Sci U S Aauthors
Polo JM,Juszczynski P,Monti S,Cerchietti L,Ye K,Greally JM,Shipp M,Melnick Adoi
10.1073/pnas.0611399104subject
Has Abstractpub_date
2007-02-27 00:00:00pages
3207-12issue
9eissn
0027-8424issn
1091-6490pii
0611399104journal_volume
104pub_type
杂志文章abstract::The effect of RNA secondary structure on rho-independent and rho-dependent termination of transcription of T3 DNA by Escherichia coli RNA polymerase has been studied by incorporating, into nascent transcripts, base analogs that lead to altered base-pairing properties. A guanine --> hypoxanthine substitution, with atte...
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.76.4.1613
更新日期:1979-04-01 00:00:00
abstract::Transcriptional network evolution is central to the development of complex biological systems. Networks can evolve through variation of master regulators and/or by changes in regulation of genes within networks. To gain insight into meaningful evolutionary differences in large networks, it is essential to address the ...
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.0704694105
更新日期:2008-01-22 00:00:00
abstract::Most paleo-episodes of ocean acidification (OA) were either too slow or too small to be instructive in predicting near-future impacts. The end-Cretaceous event (66 Mya) is intriguing in this regard, both because of its rapid onset and also because many pelagic calcifying species (including 100% of ammonites and more t...
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.1418604112
更新日期:2015-05-26 00:00:00
abstract::We use a three-dimensional, higher-order ice flow model and a realistic initial condition to simulate dynamic perturbations to the Greenland ice sheet during the last decade and to assess their contribution to sea level by 2100. Starting from our initial condition, we apply a time series of observationally constrained...
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.1017313108
更新日期:2011-05-31 00:00:00
abstract::The most common monogenic cause of small-vessel disease leading to ischemic stroke and vascular dementia is the neurodegenerative syndrome cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), which is associated with mutations in the Notch 3 receptor. CADASIL pathology ...
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.1101964108
更新日期:2011-05-24 00:00:00
abstract::To determine which of seven library design algorithms best introduces new protein function without destroying it altogether, seven combinatorial libraries of green fluorescent protein variants were designed and synthesized. Each was evaluated by distributions of emission intensity and color compiled from measurements ...
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.0609647103
更新日期:2007-01-02 00:00:00
abstract::Hepatitis C virus subverts liver-specific microRNA, miR-122, to upregulate viral RNA abundance in both infected cultured cells and in the liver of infected chimpanzees. These findings have identified miR-122 as an attractive antiviral target. Thus, it is imperative to know whether a distinct functional complex exists ...
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.1012464108
更新日期:2011-02-22 00:00:00
abstract::Fluorescence in situ hybridization (FISH) resolution has advanced because newer techniques use increasingly decondensed chromatin. FISH cannot analyze restriction enzyme cutting sites due to limitations of the hybridization and detection technologies. The RecA-assisted restriction endonuclease (RARE) technique cleaves...
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.92.1.165
更新日期:1995-01-03 00:00:00
abstract::Mood disorders cause much suffering and are the single greatest cause of lost productivity worldwide. Although multiple medications, along with behavioral therapies, have proven effective for some individuals, millions of people lack an effective therapeutic option. A common serotonin (5-HT) transporter (5-HTT/SERT, 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.0800466105
更新日期:2008-12-02 00:00:00
abstract::Energy transfer is enhanced by translational diffusion of the donor and acceptor [Steinberg, I. Z. & Katchalski, E. (1968) J. Chem. Phys. 48, 2404-2410]. The effect of diffusion on energy transfer depends on Dtau(0)/s(2), in which D is the sum of the diffusion coefficients of the donor and acceptor, tau(0) is the life...
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.75.12.5746
更新日期:1978-12-01 00:00:00
abstract::For almost a century, alcohols have been thought to produce their effects by actions on the membrane lipids of central nervous system neurons--the well known "lipid theory" of alcohol action. The rationale for this theory is the correlation of potency with oil/water or membrane/buffer partition coefficient. Although a...
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.91.17.8200
更新日期:1994-08-16 00:00:00
abstract::The sequence of the transforming region of simian sarcoma virus (SSV) has been determined by using molecularly cloned viral DNA. This region encompassed the 1.0-kilobase pair woolly monkey cell-derived insertion sequence, v-sis, and flanking simian sarcoma-associated viral (SSAV) sequences. A 675-nucleotide-long open ...
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.79.10.3179
更新日期:1982-05-01 00:00:00
abstract::Innate immunity can facilitate nervous system regeneration, yet the underlying cellular and molecular mechanisms are not well understood. Here we show that intraocular injection of lipopolysaccharide (LPS), a bacterial cell wall component, or the fungal cell wall extract zymosan both lead to rapid and comparable intra...
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.1423221112
更新日期:2015-02-24 00:00:00
abstract::We isolated mutant strains of the facultative anaerobe Salmonella typhimurium that grow either aerobically or anaerobically. Strict anaerobic mutants contained a defective DNA topoisomerase I gene (topI), while strict aerobic mutants contained a defective DNA gyrase subunit A gene (gyrA, also nalA). Topoisomerase I ac...
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.82.7.2077
更新日期:1985-04-01 00:00:00
abstract::Wild-type Escherichia coli cells grow normally in 95% O(2)/5% CO(2). In contrast, cells that cannot make polyamines because of mutations in the biosynthetic pathway are rapidly killed by incubation in 95% O(2)/5% CO(2). Addition of polyamines prevents the toxic effect of oxygen, permitting cell survival and optimal gr...
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.2627990100
更新日期:2003-03-04 00:00:00
abstract::Transfection of cells with the H-2Kk gene lacking the transmembrane and cytoplasmic segments resulted in secretion of the H-2Kk protein, as determined by immunoprecipitation with monoclonal anti-H-2Kk antibodies. Transgenic (H-2b X H-2d)F1 mice were established carrying integrated copies of the modified H-2Kk gene. Ex...
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.85.7.2269
更新日期:1988-04-01 00:00:00
abstract::A synchronized heart beat is controlled by pacemaking impulses conducted through Purkinje fibers. In chicks, these impulse-conducting cells are recruited during embryogenesis from myocytes in direct association with developing coronary arteries. In culture, the vascular cytokine endothelin converts embryonic myocytes ...
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.96.23.13214
更新日期:1999-11-09 00:00:00
abstract::Soluble, glutathione-stimulated delta 5-3-ketosteroid isomerase (EC 5.3.3.A) activity of human and rat liver resides in very basic proteins with molecular weights of about 45,000 which are present in high concentrations in these tissues. Physiochemical and immunological evidence is presented for the identity of the 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.74.1.158
更新日期:1977-01-01 00:00:00
abstract::The central nervous system both influences and is influenced by the gastrointestinal system. Most research on this gut-brain connection has focused on how ascending signals from the gut and its microbiome alter brain function. Less attention has focused on how descending signals from the central nervous system alter g...
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.2002737117
更新日期:2020-06-09 00:00:00
abstract::The mathematical theory of compressed sensing (CS) asserts that one can acquire signals from measurements whose rate is much lower than the total bandwidth. Whereas the CS theory is now well developed, challenges concerning hardware implementations of CS-based acquisition devices--especially in optics--have only start...
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.1119511109
更新日期:2012-06-26 00:00:00
abstract::Understanding biological and physical processes involving nucleic acids, such as the binding of proteins to DNA and RNA, DNA condensation, and RNA folding, requires an understanding of the ion atmosphere that surrounds nucleic acids. We have used a simple model DNA system to determine how the ion atmosphere modulates ...
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.0404448102
更新日期:2005-01-25 00:00:00
abstract::The human amygdala plays a key role in recognizing facial emotions and neurons in the monkey and human amygdala respond to the emotional expression of faces. However, it remains unknown whether these responses are driven primarily by properties of the stimulus or by the perceptual judgments of the perceiver. We invest...
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
doi:10.1073/pnas.1323342111
更新日期:2014-07-29 00:00:00
abstract::The catalytic activity of low-dimensional electrocatalysts is highly dependent on their local atomic structures, particularly those less-coordinated sites found at edges and corners; therefore, a direct probe of the electrocatalytic current at specified local sites with true nanoscopic resolution has become critically...
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.1821091116
更新日期:2019-06-11 00:00:00
abstract::Burkitt's lymphomas, linked by previous studies with the DNA-containing Epstein-Barr virus, contain an RNA related in sequence to that of Rauscher leukemia virus. The present study establishes that the viral-related RNA found in Burkitt's tumors is a 70S component encapsulated with RNA-instructed DNA polymerase in a 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.70.3.737
更新日期:1973-03-01 00:00:00
abstract::In this study, we compared the transport of newly synthesized cholesterol with that of influenza virus hemagglutinin (HA) from the endoplasmic reticulum to the plasma membrane. The arrival of cholesterol on the cell surface was monitored by cyclodextrin removal, and HA transport was monitored by surface trypsinization...
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.140218797
更新日期:2000-07-18 00:00:00
abstract::Evidence for perceptual periodicity emerges from studies showing periodic fluctuations in visual perception and decision making that are accompanied by neural oscillations in brain activity. We have uncovered signs of periodicity in the time course of binocular rivalry, a widely studied form of multistable perception....
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.1905174116
更新日期:2019-07-23 00:00:00
abstract::Observations from human microbiome studies are often conflicting or inconclusive. Many factors likely contribute to these issues including small cohort sizes, sample collection, and handling and processing differences. The field of microbiome research is moving from 16S rDNA gene sequencing to a more comprehensive gen...
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.1519288112
更新日期:2015-11-10 00:00:00
abstract::Many "workers" in north temperate colonies of the eusocial paper wasp Polistes fuscatus disappear within a few days of eclosion. We provide evidence that these females are pursuing an alternative reproductive strategy, i.e., dispersing to overwinter and become nest foundresses the following spring, instead of helping ...
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.95.23.13737
更新日期:1998-11-10 00:00:00
abstract::We present here the complete genome sequence of a common avian clone of Pasteurella multocida, Pm70. The genome of Pm70 is a single circular chromosome 2,257,487 base pairs in length and contains 2,014 predicted coding regions, 6 ribosomal RNA operons, and 57 tRNAs. Genome-scale evolutionary analyses based on pairwise...
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.051634598
更新日期:2001-03-13 00:00:00
abstract::The structure of HIV-1 Psi-RNA has been elucidated by a concerted approach combining structural probes with mass spectrometric detection (MS3D), which is not affected by the size and crystallization properties of target biomolecules. Distance constraints from bifunctional cross-linkers provided the information require...
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.0800509105
更新日期:2008-08-26 00:00:00