Abstract:
:Accumulating evidence suggests cancer cells exhibit a dependency on metabolic pathways regulated by nicotinamide adenine dinucleotide (NAD+). Nevertheless, how the regulation of this metabolic cofactor interfaces with signal transduction networks remains poorly understood in glioblastoma. Here, we report nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in NAD+ synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells (GSCs). High NAMPT expression in tumors correlates with decreased patient survival. Pharmacological and genetic inhibition of NAMPT decreased NAD+ levels and GSC self-renewal capacity, and NAMPT knockdown inhibited the in vivo tumorigenicity of GSCs. Regulatory network analysis of RNA sequencing data using GSCs treated with NAMPT inhibitor identified transcription factor E2F2 as the center of a transcriptional hub in the NAD+-dependent network. Accordingly, we demonstrate E2F2 is required for GSC self-renewal. Downstream, E2F2 drives the transcription of members of the inhibitor of differentiation (ID) helix-loop-helix gene family. Finally, we find NAMPT mediates GSC radiation resistance. The identification of a NAMPT-E2F2-ID axis establishes a link between NAD+ metabolism and a self-renewal transcriptional program in glioblastoma, with therapeutic implications for this formidable cancer.
journal_name
Proc Natl Acad Sci U S Aauthors
Gujar AD,Le S,Mao DD,Dadey DY,Turski A,Sasaki Y,Aum D,Luo J,Dahiya S,Yuan L,Rich KM,Milbrandt J,Hallahan DE,Yano H,Tran DD,Kim AHdoi
10.1073/pnas.1610921114subject
Has Abstractpub_date
2016-12-20 00:00:00pages
E8247-E8256issue
51eissn
0027-8424issn
1091-6490pii
1610921114journal_volume
113pub_type
杂志文章abstract::The primate visual motion system performs numerous functions essential for survival in a dynamic visual world. Prominent among these functions is the ability to recover and represent the trajectories of objects in a form that facilitates behavioral responses to those movements. The first step toward this goal, which c...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章,评审
doi:10.1073/pnas.92.7.2433
更新日期:1995-03-28 00:00:00
abstract::Based on the cell surface expression of CD4 and CD8 molecules, murine thymocytes can be divided into four populations: these include CD4-, CD8- double-negative and CD4+, CD8+ double-positive subpopulations, both of which consist largely of immature cells, and the single positive, CD4+ or CD8+, subsets that contain fun...
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.85.22.8633
更新日期:1988-11-01 00:00:00
abstract::All available complete mitochondrial genomes (21 species) are evaluated for dinucleotide over- and under-representation. The CpG dinucleotide is pervasively under-represented in all animal mitochondria, but it is of variable relative abundance in fungal, protist, and plant mitochondrial genomes. Interpretations and hy...
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.91.9.3799
更新日期:1994-04-26 00:00:00
abstract::Many thylakoid lumen proteins are synthesized outside the chloroplast as larger molecular weight precursors and then processed to their mature size during transport to the lumenal space. We have examined the post-translational processing of thylakoid lumen proteins in vivo by pulse-radiolabeling experiments with Chlam...
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.90.5.1862
更新日期:1993-03-01 00:00:00
abstract::G proteins are activated when they associate with G protein-coupled receptors (GPCRs), often in response to agonist-mediated receptor activation. It is generally thought that agonist-induced receptor-G protein association necessarily promotes G protein activation and, conversely, that activated GPCRs do not interact w...
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.2003787117
更新日期:2020-09-01 00:00:00
abstract::Assembly of nitrogenase FeMoco is one of the key processes in bioinorganic chemistry. NifB and NifEN are two essential elements immediately adjacent to each other along the biosynthetic pathway of FeMoco. Previously, an 8Fe-precursor of FeMoco was identified on NifEN; however, the identity of the biosynthetic intermed...
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.1102773108
更新日期:2011-05-24 00:00:00
abstract::Antigen receptors on the T-cell surface are noncovalently associated with at least four invariant polypeptide chains, CD3-gamma, -delta, -epsilon, and -zeta. The mouse CD3-gamma gene, consisting of seven exons, was found to be highly homologous to the CD3-delta gene described earlier. Both the high level of sequence 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.84.24.9131
更新日期:1987-12-01 00:00:00
abstract::RNA interference (RNAi) is a widely used method for analysis of gene function in tissue culture cells. However, to date there has been no reliable method for testing the specificity of any particular RNAi experiment. The ideal experiment is to rescue the phenotype by expression of the target gene in a form refractory ...
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.0409861102
更新日期:2005-02-15 00:00:00
abstract::The combination of catalytic amounts of optically active dipyridylphosphine and CuF(2) along with hydride donor PhSiH(3) generated in situ a remarkably reactive catalyst system (substrate-to-ligand molar ratio up to 100,000) for the highly enantioselective hydrosilylation of a broad spectrum of aryl alkyl ketones (up ...
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.0409043102
更新日期:2005-03-08 00:00:00
abstract::Glioblastoma multiforme (GBM) is one of the most intractable of human cancers, principally because of the highly infiltrative nature of these neoplasms. Tracking and eradicating infiltrating GBM cells and tumor microsatellites is of utmost importance for the treatment of this devastating disease, yet effective strateg...
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.1615396113
更新日期:2016-11-29 00:00:00
abstract::Chloroplast DNA (cpDNA) is under great photooxidative stress, yet its evolution is very conservative compared with nuclear or mitochondrial genomes. It can be expected that DNA repair mechanisms play important roles in cpDNA survival and evolution, but they are poorly understood. To gain insight into how the most seve...
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.1004326107
更新日期:2010-08-03 00:00:00
abstract::Parkinson's disease (PD) is a neurodegenerative disorder of uncertain pathogenesis characterized by a loss of substantia nigra pars compacta (SNpc) dopaminergic (DA) neurons, and can be modeled by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Both inflammatory processes and oxidative stress may 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.0937239100
更新日期:2003-05-13 00:00:00
abstract::Individual cell types are defined by architecturally and functionally specialized cortical domains. The Ezrin, Radixin, and Moesin (ERM) proteins play a major role in organizing cortical domains by assembling membrane protein complexes and linking them to the cortical actin cytoskeleton. Many studies have focused on 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.1103418108
更新日期:2011-07-19 00:00:00
abstract::A monoclonal antibody was produced to human peripheral blood T cells. This hybridoma antibody, termed OKT4, was reactive by indirect immunofluorescence with only 55-60% of the peripheral blood T cell population (OKT4+) and unreactive with normal B cells, null cells, and macrophages. The OKT4- T cell population contain...
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.76.8.4061
更新日期:1979-08-01 00:00:00
abstract::The transforming growth factor-beta (TGF-beta) superfamily of growth factors and cytokines has been implicated in a variety of physiological and developmental processes within the cardiovascular system. Smad proteins are a recently described family of intracellular signaling proteins that transduce signals in response...
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.95.16.9506
更新日期:1998-08-04 00:00:00
abstract::High-resolution analyses of a late Holocene core from Kettle Lake in North Dakota reveal coeval fluctuations in loss-on-ignition carbonate content, percentage of grass pollen, and charcoal flux. These oscillations are indicative of climate-fuel-fire cycles that have prevailed on the Northern Great Plains (NGP) for mos...
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.0503621102
更新日期:2005-06-21 00:00:00
abstract::In 1999, the population of Vancouver Island, Canada, began to experience an outbreak of a fatal fungal disease caused by a highly virulent lineage of Cryptococcus gattii. This organism has recently spread to the Canadian mainland and Pacific Northwest, but the molecular cause of the outbreak remains unknown. Here we 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.0902963106
更新日期:2009-08-04 00:00:00
abstract::The major cell surface glycoconjugate of Leishmania major, a putative parasite receptor for macrophages, is a lipophosphoglycan containing 81.6% (wt/wt) carbohydrate, 17.0% (wt/wt) phosphate, and 1.4% (wt/wt) lipid. It has been purified to homogeneity by hydrophobic chromatography and consists of a polydisperse family...
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.84.24.8941
更新日期:1987-12-01 00:00:00
abstract::Pancreatic islets regulate glucose homeostasis through coordinated actions of hormone-secreting cells. What underlies the function of the islet as a unit is the close approximation and communication among heterogeneous cell populations, but the structural mediators of islet cellular cross talk remain incompletely char...
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.2001936117
更新日期:2020-04-21 00:00:00
abstract::The theory presented here is based on results from in vitro experiments and deals with three proteins in the postsynaptic density/membrane-namely, calmodulin, the Ca2+/calmodulin-dependent protein kinase, and the voltage-dependent Ca2+ channel. It is visualized that, in vivo in the polarized state of the membrane, cal...
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.88.12.5374
更新日期:1991-06-15 00:00:00
abstract::Apomixis is a naturally occurring mode of reproduction that results in embryo formation without the involvement of meiosis or fertilization of the egg. Seed-derived progeny of an apomictic plant are genetically identical to the maternal parent. We are studying a form of apomixis called apospory that occurs in the genu...
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.95.9.5127
更新日期:1998-04-28 00:00:00
abstract::Osteocalcin, a bone-specific protein and marker of the mature osteoblast, is expressed only in nonproliferating osteoblasts in a mineralizing extracellular matrix, while type I collagen is expressed in proliferating cells. The nuclear proteins encoded by the c-fos and c-jun protooncogenes are expressed during the prol...
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.87.24.9990
更新日期:1990-12-01 00:00:00
abstract::Biochemical and genetic studies have implicated alpha-gustducin as a key component in the transduction of both bitter or sweet taste. Yet, alpha-gustducin-null mice are not completely unresponsive to bitter or sweet compounds. To gain insights into how gustducin mediates responses to bitter and sweet compounds, and 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.151235798
更新日期:2001-07-17 00:00:00
abstract::The late Pleistocene witnessed the extinction of 35 genera of North American mammals. The last appearance dates of 16 of these genera securely fall between 12,000 and 10,000 radiocarbon years ago (approximately 13,800-11,400 calendar years B.P.), although whether the absence of fossil occurrences for the remaining 19 ...
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.0908153106
更新日期:2009-12-08 00:00:00
abstract::Lipoxin B (LXB) was prepared by incubation of (15S)-15-hydroperoxy-5,8,11-cis-13-trans-icosatetraenoic acid (15-HPETE) with human leukocytes. Comparison with a number of trihydroxyicosatetraenes prepared by total synthesis showed that biologically derived LXB is (5S,14R,15S)-5,14,15-trihydroxy-6,10,12-trans-8-cis-icos...
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.83.7.1983
更新日期:1986-04-01 00:00:00
abstract::Necessary conditions are derived for a spherical vortex in a perfect fluid to be stationary in the case when the velocities depend on a single surface harmonic. The motion is indeterminate unless an additional condition is imposed. In the case when this condition is incompressibility, the equations are solved, yieldin...
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.69.9.2460
更新日期:1972-09-01 00:00:00
abstract::MXenes, a new family of 2D materials, combine hydrophilic surfaces with metallic conductivity. Delamination of MXene produces single-layer nanosheets with thickness of about a nanometer and lateral size of the order of micrometers. The high aspect ratio of delaminated MXene renders it promising nanofiller in multifunc...
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.1414215111
更新日期:2014-11-25 00:00:00
abstract::PCSK9 encodes proprotein convertase subtilisin/kexin type 9a (PCSK9), a member of the proteinase K subfamily of subtilases. Missense mutations in PCSK9 cause an autosomal dominant form of hypercholesterolemia in humans, likely due to a gain-of-function mechanism because overexpression of either WT or mutant PCSK9 redu...
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.0501652102
更新日期:2005-04-12 00:00:00
abstract::It is suggested that differentiated embryonic cells have a high specificity of molecular constitution as regards the surface layers surrounding their cellular membranes. Correspondingly, specific interface energies may characterize the early contacts between different cell types. The question is raised whether the mor...
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.67.1.156
更新日期:1970-09-01 00:00:00
abstract::We construct a C*-algebra that has only one irreducible representation up to unitary equivalence but is not isomorphic to the algebra of compact operators on any Hilbert space. This answers an old question of Naimark. Our construction uses a combinatorial statement called the diamond principle, which is known to be co...
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.0401489101
更新日期:2004-05-18 00:00:00