Abstract:
:The activity of cullin-containing ubiquitin protein ligase complexes is stimulated by linkage to cullin of the ubiquitin-like protein Nedd8 ("neddylation"). Neddylation is inhibited by the tight binding of cullins to CAND1 (cullin-associated and neddylation-dissociated 1) protein, and Nedd8 is removed from cullins by specific isopeptidase activity of the COP9/signalosome (CSN) complex. The mechanisms that regulate neddylation and deneddylation of cullins were unknown. We examined this problem for the case of SCF(Skp2), a cullin1 (Cul1)-containing ubiquitin ligase complex that contains the S phase-associated protein Skp2 as the substrate-binding F-box protein subunit. SCF(Skp2) targets for degradation the cyclin-dependent kinase (cdk) inhibitor p27 in the G(1)-to-S phase transition, a process that requires its phosphorylation and binding to cdk2-cyclin E. Because levels of Skp2, cyclin E, and the accessory protein Cks1 (cyclin kinase subunit 1) all rise at the end of G(1) phase, it seemed possible that the neddylation of Cul1 in SCF(Skp2) is regulated by the availability of the F-box protein and/or the substrate. We found that the supplementation of Skp2-Skp1 and substrate (along with further components necessary for substrate presentation to the ubiquitin ligase) to extracts of HeLa cells synergistically increased levels of neddylated Cul1. Skp2-Skp1 abrogates the inhibitory influence of CAND1 on the neddylation of Cul1 by promoting the dissociation of the cullin-CAND1 complex, whereas substrate, together with substrate-presenting components, prevents the action of CSN to deneddylate cullin. We propose a sequence of events in which the increased availability of Skp2 and substrate in the transition of cells to S phase promotes the neddylation and assembly of the SCF(Skp2) ubiquitin ligase complex.
journal_name
Proc Natl Acad Sci U S Aauthors
Bornstein G,Ganoth D,Hershko Adoi
10.1073/pnas.0603921103subject
Has Abstractpub_date
2006-08-01 00:00:00pages
11515-20issue
31eissn
0027-8424issn
1091-6490pii
0603921103journal_volume
103pub_type
杂志文章abstract::Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by early pre-B phenotype (CD10(-)/CD19(+)) and poor treatment outcome. The t(4;11), creating MLL-AF4 chimeric transcripts, is the predominant 11q23 chromosome translocation in infant ALL and is associated with extremely poor progno...
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.96.25.14535
更新日期:1999-12-07 00:00:00
abstract::CYP1B1-null mice, created by targeted gene disruption in embryonic stem cells, were born at the expected frequency from heterozygous matings with no observable phenotype, thus establishing that CYP1B1 is not required for mouse development. CYP1B1 was not detectable in cultured embryonic fibroblast (EF) or in different...
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.96.5.1977
更新日期:1999-03-02 00:00:00
abstract::Biologically active (125)I-labeled bovine parathyroid hormone (prepared by electrolytic iodination) and its synthetic NH(2)-terminal (1-34) biologically active fragment bound rapidly and specifically to a purified plasma membrane preparation from bovine renal cortex. Binding of labeled intact hormone or labeled NH(2)-...
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.71.3.723
更新日期:1974-03-01 00:00:00
abstract::Indole-3-acetic acid is the major auxin in most plants. In Cruciferae, including Brassicaceae, indole-3-acetic acid is synthesized from indole-3-acetonitrile by nitrilase, after indole-3-acetonitrile is formed from tryptophan via indole-3-acetaldoxime or indole glycosinolates as the intermediate. We cloned and sequenc...
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.90.1.247
更新日期:1993-01-01 00:00:00
abstract::We examine the IFN-alpha/beta-independent activation of cellular transcription that constitutes an early antiviral response of cells against influenza A and B viruses, which cause widespread epidemics in humans. We show that influenza B virus induces the synthesis in human cells of several mature mRNAs encoded by gene...
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.152327499
更新日期:2002-07-23 00:00:00
abstract::Alpha-Klotho (alpha-Kl) and its homolog, beta-Klotho (beta-Kl) are key regulators of mineral homeostasis and bile acid/cholesterol metabolism, respectively. FGF15/ humanFGF19, FGF21, and FGF23, members of the FGF19 subfamily, are believed to act as circulating metabolic regulators. Analyses of functional interactions ...
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.0913986107
更新日期:2010-01-26 00:00:00
abstract::Through a process called "bioturbation," burrowing macrofauna have altered the seafloor habitat and modified global carbon cycling since the Cambrian. However, the impact of macrofauna on the community structure of microorganisms is poorly understood. Here, we show that microbial communities across bioturbated, but ge...
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.1917494117
更新日期:2020-07-07 00:00:00
abstract::The expression of the adenovirus (Ad) early coding region 1a (E1a) is required for virus-induced cell transformation and for the activation of other viral early genes and some cellular genes. Two overlapping early mRNAs of 13S and 12S that are transcribed from this region code for a 289-amino acid protein and a 243-am...
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.82.1.163
更新日期:1985-01-01 00:00:00
abstract::The number of red blood cells is normally tightly regulated by a classic homeostatic mechanism based on oxygen sensing in the kidney. Decreased oxygen delivery resulting from anemia induces the production of erythropoietin, which increases red cell production and hence oxygen delivery. Investigations of erythropoietin...
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.0508423103
更新日期:2006-01-17 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::Although infection by primary HIV type 1 (HIV-1) isolates normally requires the functional interaction of the viral envelope protein with both CD4 and the CCR-5 coreceptor, a subset of such isolates also are able to use the distinct CCR-3 receptor. By analyzing the ability of a series of wild-type and chimeric HIV-1 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.95.13.7682
更新日期:1998-06-23 00:00:00
abstract::The 5'-phosphoinositol phosphatase SHIP negatively regulates signaling pathways triggered by antigen, cytokine and Fc receptors in both lymphocytes and myeloid cells. Mice with germ-line (null) deletion of SHIP develop a myeloproliferative-like syndrome that causes early lethality. Lymphocyte anomalies have been obser...
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.0704853104
更新日期:2007-07-03 00:00:00
abstract::Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, wh...
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.1717871115
更新日期:2018-01-30 00:00:00
abstract::mRNA-dependent cell-free protein synthesis systems were prepared from a heme-deficient ole3 mutant of the yeast Saccharomyces cerevisiae grown either in the absence or in the presence of the heme precursor delta-aminolevulinate. When supplemented with total yeast mRNA, the two systems-from heme-deficient and from heme...
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.79.24.7609
更新日期:1982-12-01 00:00:00
abstract::Despite the increasing number of regulatory proteins identified in clathrin-independent endocytic (CIE) pathways, our understanding of the exact functions of these proteins and the sequential manner in which they function remains limited. In this study, using the Caenorhabditis elegans intestine as a model, we observe...
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.1408327111
更新日期:2014-10-28 00:00:00
abstract::Interferon regulatory factor (IRF) 4 is a member of the IRF family of transcription factors and plays critical roles in the development of CD4(+) T cells into Th2 and Th17 cells. Using the infection model of Nippostrongyrus brasiliensis, we have confirmed the critical roles of IRF-4 in Th2 development in vivo by using...
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.0803171105
更新日期:2008-10-14 00:00:00
abstract::Parkin functions as a multipurpose E3 ubiquitin ligase, and Parkin loss of function is associated with both sporadic and familial Parkinson's disease (PD). We report that the Bin/Amphiphysin/Rvs (BAR) domain of protein interacting with PRKCA1 (PICK1) bound to the really interesting new gene 1 (RING1) domain of Parkin ...
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.1716506115
更新日期:2018-07-24 00:00:00
abstract::Identification of the consensus sequence for termination of replication (ter) in Escherichia coli and the isolation of the ter-binding protein (TBP) allowed us to test their effects on replication forks initiated at the unique origin of the E. coli chromosome (oriC) in a purified enzyme system. Replication was severel...
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.86.23.9104
更新日期:1989-12-01 00:00:00
abstract::Wild-type newborn mice are characterized by the ability of certain liver-specific genes encoding various enzymes and mapping on different chromosomes to respond to glucocorticoid induction. Newborn mice homozygous for deletions at and around the albino locus on chromosome 7 fail to develop this competence for hormone-...
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.88.13.5607
更新日期:1991-07-01 00:00:00
abstract::We have cloned and partially characterized 24 loci from the human genome which are complementary to U1, U2, or U3, the three major species of small nuclear RNA (snRNA) in HeLa cells. When compared to the known U1 (human) and U2 (rat) snRNA sequences, the DNA sequences we report here for the complementary regions from ...
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.78.2.810
更新日期:1981-02-01 00:00:00
abstract::Mobile ectothermic animals can control their body temperatures by selecting specific thermal conditions in the environment, but embryos--trapped within an immobile egg and lacking locomotor structures--have been assumed to lack that ability. Falsifying that assumption, our experimental studies show that even early sta...
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.1102965108
更新日期:2011-06-07 00:00:00
abstract::The nucleus accumbens is considered a critical target of the action of drugs of abuse. In this nucleus a "shell" and a "core" have been distinguished on the basis of anatomical and histochemical criteria. The present study investigated the effect in freely moving rats of intravenous cocaine, amphetamine, and morphine ...
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.92.26.12304
更新日期:1995-12-19 00:00:00
abstract::In 2009 we reported that depletion of Dicer-1, the enzyme that catalyzes the final step of miRNA biosynthesis, prevents metamorphosis in Blattella germanica. However, the precise regulatory roles of miRNAs in the process have remained elusive. In the present work, we have observed that Dicer-1 depletion results in an ...
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.1418522112
更新日期:2015-03-24 00:00:00
abstract::Rod signals in the mammalian retina are thought to reach ganglion cells over the circuit rod-->rod depolarizing bipolar cell-->AII amacrine cell-->cone bipolar cells-->ganglion cells. A possible alternative pathway involves gap junctions linking the rods and cones, the circuit being rod-->cone-->cone bipolar cells-->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.92.23.10658
更新日期:1995-11-07 00:00:00
abstract::The rate of leucine incorporation into a specific estrogen-induced protein of immature rat isolated by gel electrophoresis declines rapidly between 2-4 hr after estrogen stimulation in vivo followed by incubation in vitro. Actinomycin D present during the in vitro phase prevents this decline, and elicits a "superinduc...
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.70.1.18
更新日期:1973-01-01 00:00:00
abstract::cis-jasmone, or (Z)-jasmone, is well known as a component of plant volatiles, and its release can be induced by damage, for example during insect herbivory. Using the olfactory system of the lettuce aphid to investigate volatiles from plants avoided by this insect, (Z)-jasmone was found to be electrophysiologically 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.160241697
更新日期:2000-08-01 00:00:00
abstract::Mammalian homologues of Drosophila Trp form plasma membrane channels that mediate Ca(2+) influx in response to activation of phospholipase C and internal Ca(2+) store depletion. Previous studies showed that human Trp3 is activated by inositol 1,4,5-trisphosphate (IP(3)) receptors (IP(3)Rs) and identified interacting d...
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.051632698
更新日期:2001-03-13 00:00:00
abstract::Proopiomelanocortin (POMC), a major pituitary product, is also present in the adult mouse testis. We have shown previously that POMC mRNAs are most abundant in a subpopulation of Leydig cells associated with tubules in specific stages of the cycle of the seminiferous epithelium. In the present study, we examined 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.84.6.1600
更新日期:1987-03-01 00:00:00
abstract::Despite the importance of aggression in the behavioral repertoire of most animals, relatively little is known of its proximate causation and control. To take advantage of modern methods of genetic analysis for studying this complex behavior, we have developed a quantitative framework for studying aggression in common ...
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.082102599
更新日期:2002-04-16 00:00:00
abstract::Neutrinos represent a new "window" to the Universe, spanning a large range of energy. We discuss the science of neutrino astrophysics and focus on two energy regimes. At "lower" energies ( approximately 1 MeV), studies of neutrinos born inside the sun, or produced in interactions of cosmic rays with the atmosphere, ha...
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.96.25.14201
更新日期:1999-12-07 00:00:00