Abstract:
:Wnt signaling regulates many aspects of development by increasing the signaling activity of beta-catenin. Axin is a negative regulator of the Wnt signaling pathway, and it is responsible for the formation of the beta-catenin degradation complex. Genetic studies with Drosophila suggest that Axin promotes cytoplasmic localization of beta-catenin independent of Axin's known role of enhancing degradation of beta-catenin. Here, we show that Axin is a nuclear-cytoplasmic shuttling protein. Nuclear export of Axin depends on the chromosome maintenance region 1 nuclear receptor; treatment with the chromosome maintenance region 1 inhibitor leptomycin B induces nuclear accumulation of ectopically expressed or endogenous Axin. Functional nuclear localization and nuclear export signals have been mapped within Axin. Significantly, overexpression of an Axin fragment shifts coexpressed stabilized beta-catenin to the cytoplasm, and this effect requires shuttling of Axin between the cytoplasm and the nucleus. Our results suggest that Axin functions as a molecular chaperone for beta-catenin and that nuclear-cytoplasmic shuttling of Axin regulates the nuclear-cytoplasmic distribution of beta-catenin.
journal_name
Proc Natl Acad Sci U S Aauthors
Cong F,Varmus Hdoi
10.1073/pnas.0307344101keywords:
subject
Has Abstractpub_date
2004-03-02 00:00:00pages
2882-7issue
9eissn
0027-8424issn
1091-6490pii
0307344101journal_volume
101pub_type
杂志文章abstract::The human eosinophil differentiation factor (EDF) gene was cloned from a genomic library in lambda phage EMBL3A by using a murine EDF cDNA clone as a probe. The DNA sequence of a 3.2-kilobase BamHI fragment spanning the gene was determined. The gene contains three introns. The predicted amino acid sequence of 134 amin...
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.84.19.6629
更新日期:1987-10-01 00:00:00
abstract::We used a model system of purified components to explore the effects of a downstream target on the signaling properties of a covalent modification cycle, an example of retroactivity. In the experimental system used, a bifunctional enzyme catalyzed the modification and demodification of its substrate protein, with both...
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.0913815107
更新日期:2010-06-01 00:00:00
abstract::A major challenge in interpreting genome sequences is understanding how the genome encodes the information that specifies when and where a gene will be expressed. The first step in this process is the identification of regions of the genome that contain regulatory information. In higher eukaryotes, this cis-regulatory...
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.231608898
更新日期:2002-01-22 00:00:00
abstract::Ciliary Neurotrophic Factor (CNTF) was first characterized as a trophic factor for motor neurons in the ciliary ganglion and spinal cord, leading to its evaluation in humans suffering from motor neuron disease. In these trials, CNTF caused unexpected and substantial weight loss, raising concerns that it might produce ...
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.061034298
更新日期:2001-04-10 00:00:00
abstract::Dimerization of human immunodeficiency virus type 1 protease (HIV-1 PR) monomers is an essential prerequisite for viral proteolytic activity and the subsequent generation of infectious virus particles. Disruption of the dimer interface inhibits this activity as does formation of heterodimers between wild-type and defe...
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.93.21.11477
更新日期:1996-10-15 00:00:00
abstract::Portable, single-sided NMR sensors can operate under conditions inaccessible to conventional NMR while featuring lower cost, portability, and the ability to analyze arbitrary-sized objects. Such sensors can nondestructively probe the interior of samples by collecting images and measuring relaxation and diffusion const...
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.0811222106
更新日期:2008-12-30 00:00:00
abstract::GLQ223 is a highly purified, formulated preparation of trichosanthin, a 26-kDa plant-derived ribosome-inactivating protein with potent inhibitory activity against human immunodeficiency virus (HIV) in vitro. The compound produced concentration-dependent inhibition of HIV replication in acutely infected cultures of T-l...
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.86.8.2844
更新日期:1989-04-01 00:00:00
abstract::Unlike other cation channels, each subunit of most transient receptor potential (TRP) channels has an additional TRP-domain helix with an invariant tryptophan immediately trailing the gate-bearing S6. Recent cryo-electron microscopy of TRP vanilloid subfamily, member 1 structures revealed that this domain is a five-tu...
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.1502366112
更新日期:2015-03-17 00:00:00
abstract::To modify the lac permease of Escherichia coli for fluorescence spectroscopy, six tryptophan residues at positions 10, 33, 78, 151, 171, and 223 were first replaced individually with phenylalanine by using oligonucleotide-directed site-specific mutagenesis. None of the tryptophan residues is critical for activity, as ...
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.87.5.1638
更新日期:1990-03-01 00:00:00
abstract::Natural killer (NK) cells provide in vivo control of orthopoxvirus infections in association with their expansion in the draining lymph node (LN), where they are normally very rare. The mechanism of this expansion is unclear. Herein, we determined that NK-cell depletion results in enhanced infection following footpad ...
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.1220456110
更新日期:2013-01-02 00:00:00
abstract::Two approaches have been explored for the synthesis of double-stranded DNA from single-stranded DNA template complementary to rabbit 9S globin mRNA (cDNA). (i) cDNA was elongated with dCMP or dTMP homopolymeric tracts using terminal deoxynucleotidyltransferase (EC 2.7.7.31; nucleosidetriphosphate:DNA deoxynucleotidyle...
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.73.10.3418
更新日期:1976-10-01 00:00:00
abstract::Independent transgene insertions differ in expression based on their location in the genome; these position effects are of interest because they reflect the influence of genome organization on gene regulation. Position effects also represent potentially insurmountable obstacles to the rigorous functional comparison 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.95.26.15513
更新日期:1998-12-22 00:00:00
abstract::Several recombinant cowpox viruses were constructed and used to identify a viral gene that controls the production of hemorrhage in lesions caused by the Brighton Red strain of cowpox virus (CPV-BR). This gene is located in the KpnD fragment of CPV-BR DNA, between 31 and 32 kilobases from the end of the genome. This 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.83.20.7698
更新日期:1986-10-01 00:00:00
abstract::We used gene knockout mice to explore the role of Angiopoietin-like-4 (Angptl4) in lipid metabolism as well as to generate anti-Angptl4 mAbs with pharmacological activity. Angptl4 -/- mice had lower triglyceride (TG) levels resulting both from increased very low-density lipoprotein (VLDL) clearance and decreased VLDL ...
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.0705041104
更新日期:2007-07-10 00:00:00
abstract::Massive datasets that capture human movements and social interactions have catalyzed rapid advances in our quantitative understanding of human behavior during the past years. One important aspect affecting both areas is the critical role space plays. Indeed, growing evidence suggests both our movements and communicati...
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.1525443113
更新日期:2016-06-28 00:00:00
abstract::Natural exposure to prion disease is likely to occur throughout successive challenges, yet most experiments focus on single large doses of infectious material. We analyze the results from an experiment in which rodents were exposed to multiple doses of feed contaminated with the scrapie agent. We formally define hypot...
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.1833677100
更新日期:2003-09-16 00:00:00
abstract::Treatment of full-thickness damage to hyaline cartilage is hampered by the limited availability of autologous healthy cartilage and the lengthy, cost-prohibitive cell isolation and expansion steps associated with autologous cartilage implantation (ACI). Here we report a strategy for de novo engineering of ectopic auto...
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.0907774107
更新日期:2010-02-23 00:00:00
abstract::Clonal deletion provides an important mechanism for the elimination of autoreactive T cells. Deletion is accomplished by programmed cell death directed by interaction of the T-cell receptor (TCR) of the developing thymocyte with major histocompatibility complex elements in the thymic environment. In this report we pre...
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.88.6.2151
更新日期:1991-03-15 00:00:00
abstract::Myosin X (MyoX), encoded by Myo10, is a representative member of the MyTH4-FERM domain-containing myosins, and this family of unconventional myosins shares common functions in promoting formation of filopodia/stereocilia structures in many cell types with unknown mechanisms. Here, we present the structure of the MyoX ...
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.1016567108
更新日期:2011-03-01 00:00:00
abstract::The DNA adducts formed during incubation of the hepatocarcinogen N-hydroxy-2-acetylaminofluorene with Salmonella typhimurium tester strain TA1538 were investigated to determine if the covalently bound products were identical to those adducts found in rat liver DNA and to establish the biological significance of the ad...
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.79.17.5175
更新日期:1982-09-01 00:00:00
abstract::The eukaryotic DNA sliding clamp that keeps DNA polymerase engaged at a replication fork, called proliferating cell nuclear antigen (PCNA), is loaded onto the 3' ends of primer DNA through its interaction with a heteropentameric protein complex called replication factor C (RFC). The ATPase activity of RFC is necessary...
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.97.26.14127
更新日期:2000-12-19 00:00:00
abstract::Infection is a major complication of implantable medical devices, which provide a scaffold for biofilm formation, thereby reducing susceptibility to antibiotics and complicating treatment. Hematogenous implant-related infections following bacteremia are particularly problematic because they can occur at any time in 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.1703427114
更新日期:2017-06-27 00:00:00
abstract::ES cells represent a valuable model for investigating early embryo development and hold promise for future regenerative medicine strategies. The self-renewal of pluripotent mouse ES cells has been shown to require extrinsic stimulation by the bone morphogenetic protein (BMP) and leukemia inhibitory factor signaling pa...
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.0506945103
更新日期:2006-07-05 00:00:00
abstract::A crucial step in recent theories of human origins is the emergence of strong pair-bonding between males and females accompanied by a dramatic reduction in the male-to-male conflict over mating and an increased investment in offspring. How such a transition from promiscuity to pair-bonding could be achieved is puzzlin...
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.1200717109
更新日期:2012-06-19 00:00:00
abstract::Cl- channels in the apical membranes of salt-secreting epithelia are activated by both cAMP and Ca2+ second-messenger systems, and dysfunctions in their hormonal regulation have been demonstrated in patients with cystic fibrosis. We have transfected the epithelial cell line T84 with an expression vector containing a 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.87.22.8975
更新日期:1990-11-01 00:00:00
abstract::Arachidonic acid (AA) metabolites derived from both cyclooxygenase (COX) and lipoxygenase (LOX) pathways transduce a variety of signals related to cell growth. Here, we report that the AA LOX pathway also functions as a critical regulator of cell survival and apoptosis. Rat Walker 256 (W256) carcinosarcoma cells expre...
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.93.11.5241
更新日期:1996-05-28 00:00:00
abstract::The biosynthesis of specific polypeptides directed by purified viral messenger RNA from JLS-V9 cells infected with Rauscher leukemia virus has been studied in a rabbit reticulocyte lysate. The 35S viral mRNA gives rise to two major products of 65,000 and 72,000 molecular weight. The synthesis of specific polypeptides ...
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.73.2.356
更新日期:1976-02-01 00:00:00
abstract::The photosystem II (PSII) subunit S (PsbS) plays a key role in nonphotochemical quenching, a photoprotective mechanism for dissipation of excess excitation energy in plants. The precise function of PsbS in nonphotochemical quenching is unknown. By reconstituting PsbS together with the major light-harvesting complex 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.1205561110
更新日期:2013-04-02 00:00:00
abstract::We have developed human cervicovaginal organ culture systems to examine the initiating events in HIV transmission after exposure to various sources of HIV infectivity, including semen. Newly infected cells were detected in the cervical submucosa 3-4 days after exposure to a primary HIV isolate. At earlier times, exten...
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.0500848102
更新日期:2005-08-09 00:00:00
abstract::Signal transduction pathways activated by chemoattractants have been extensively studied, but little is known about the events mediating responses to mechanical stimuli. We discovered that acute mechanical perturbation of cells triggered transient activation of all tested components of the chemotactic signal transduct...
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.1608767113
更新日期:2016-11-22 00:00:00