Abstract:
:NFATc (a member of the family of nuclear factors of activated T cells) is a transcriptional factor responsible for the Ca(2+)-inducible activation of cytokine genes during the immune response. In resting T cells, NFATc is retained in the cytoplasm by a mechanism that depends on multiple phosphorylations in an N-terminal regulatory domain. Physical interaction with and dephosphorylation by Ca(2+)-activated calcineurin (Cn) allows the protein to enter the nucleus, where it binds to specific sites in cytokine gene promoters. Previous studies had identified a peptide segment in NFATc that binds Cn stably. Here we report the identification of a second Cn-binding element in NFATc, which synergizes with the previously identified element. Although these sequences are conserved in all isoforms of NFAT, we find that the two sites contribute differentially to the overall affinity for Cn in an isoform-dependent manner. The regulatory domain of NFAT also was found to be entirely devoid of structure, both in the phosphorylated and unphosphorylated state. This finding suggests that the NFAT regulatory domain does not undergo phosphorylation-induced conformational switching, but instead requires partner proteins to control accessibility of the NFAT nuclear localization and nuclear export signals.
journal_name
Proc Natl Acad Sci U S Aauthors
Park S,Uesugi M,Verdine GLdoi
10.1073/pnas.97.13.7130keywords:
subject
Has Abstractpub_date
2000-06-20 00:00:00pages
7130-5issue
13eissn
0027-8424issn
1091-6490pii
97/13/7130journal_volume
97pub_type
杂志文章abstract::Thresholds are frequently thought to be involved in the development of discrete structures in response to a shallow, monotonic gradient of morphogenetic information. We propose a mechanism for threshold setting that incorporates two essential components: (i) determinator genes that produce intracellular "determinators...
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.83.3.679
更新日期:1986-02-01 00:00:00
abstract::We have isolated, cloned, and expressed a male antennae-specific pheromone-degrading enzyme (PDE) [Antheraea polyphemus PDE (ApolPDE), formerly known as Sensillar Esterase] from the wild silkmoth, A. polyphemus, which seems essential for the rapid inactivation of pheromone during flight. The onset of enzymatic activit...
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.0505340102
更新日期:2005-09-27 00:00:00
abstract::A method is presented for variational calculation of the energy and the spin densities derived from a single-determinant wavefunction. Sum and difference coordinates [unk]R = (1/2)([unk]r(1) + [unk]r(1)) and [unk]r = [unk]r(1) - [unk]r(1) are introduced, and the density matrix P([unk]r(1),[unk]r(1)) is expanded in par...
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.77.11.6293
更新日期:1980-11-01 00:00:00
abstract::Thalassemia is a heritable human anemia caused by a variety of mutations that affect expression of the alpha- or the beta-chain of hemoglobin. The expressivity of the phenotype is likely to be influenced by unlinked modifying genes. Indeed, by using a mouse model of alpha-thalassemia, we find that its phenotype is str...
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.96.11.6291
更新日期:1999-05-25 00:00:00
abstract::Secondary organic aerosol (SOA) comprises a significant portion of atmospheric particular matter. The impact of particular matter on both human health and global climate has long been recognized. Despite its importance, there are still many unanswered questions regarding the formation and evolution of SOA in the atmos...
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.0911244107
更新日期:2010-04-13 00:00:00
abstract::An invariant substructure that forms two interlocked pairs of neighboring beta-strands occurs in essentially all known sandwich-like proteins. Eight conserved positions in these strands were recently shown to act as structural determinants. To test whether the residues at these invariant positions are conserved for me...
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.0501038102
更新日期:2005-03-15 00:00:00
abstract::Understanding nuclear receptor signaling in vivo would be facilitated by an efficient methodology to determine where a nuclear receptor is active. Herein, we present a feedback-inducible expression system in transgenic mice to detect activated nuclear receptor effector proteins by using an inducible reporter gene. Wit...
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.96.23.13270
更新日期:1999-11-09 00:00:00
abstract::Mitochondrial protein kinases (mPKs) are molecular switches that down-regulate the oxidation of branched-chain alpha-ketoacids and pyruvate. Elevated levels of these metabolites are implicated in disease states such as insulin-resistant Type II diabetes, branched-chain ketoaciduria, and primary lactic acidosis. We rep...
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.201220098
更新日期:2001-09-25 00:00:00
abstract::Full activation of T cells requires signaling through the T-cell antigen receptor (TCR) and additional surface molecules interacting with ligands on the antigen-presenting cell. TCR recognition of agonist ligands in the absence of accessory signals frequently results in the induction of a state of unresponsiveness ter...
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.93.18.9736
更新日期:1996-09-03 00:00:00
abstract::The zinc finger transcription factor Miz1 is a negative regulator of TNFalpha-induced JNK activation and cell death through inhibition of TRAF2 K63-polyubiquitination in a transcription-independent manner. Upon TNFalpha stimulation, Miz1 undergoes K48-linked polyubiquitination and proteasomal degradation, thereby reli...
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.0913690107
更新日期:2010-07-27 00:00:00
abstract::We found that two markers of differentiation, tyrosinase (monophenol, dihydroxyphenylalanine:oxygen oxidoreductase, EC 1.14.18.1) activity and melanin synthesis, are induced by diazepam in B16/C3 mouse melanoma cells. We also demonstrated high-affinity binding sites for [3H]diazepam in these cells by radioreceptor ass...
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.78.6.3935
更新日期:1981-06-01 00:00:00
abstract::Most natural populations are affected by seasonal changes in temperature, rainfall, or resource availability. Seasonally fluctuating selection could potentially make a large contribution to maintaining genetic polymorphism in populations. However, previous theory suggests that the conditions for multilocus polymorphis...
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.1702994114
更新日期:2017-11-14 00:00:00
abstract::Detection and avoidance of impending obstacles is crucial to preventing head and body injuries in daily life. To safely avoid obstacles, locations of objects approaching the body surface are usually detected via the visual system and then used by the motor system to guide defensive movements. Mediating between visual ...
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.1207946109
更新日期:2012-10-30 00:00:00
abstract::Severe combined immunodeficient (SCID) mice display an increased sensitivity to ionizing radiation compared with the parental, C.B-17, strain due to a deficiency in DNA double-strand break repair. The catalytic subunit of DNA-dependent protein kinase (DNA-PKCS) has previously been identified as a strong candidate for ...
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.93.24.13825
更新日期:1996-11-26 00:00:00
abstract::Reestablishment of vascular homeostasis following ex vivo preservation is a critical determinant of successful organ transplantation. Because the nitric oxide (NO) pathway modulates pulmonary vascular tone and leukocyte/endothelial interactions, we hypothesized that reactive oxygen intermediates would lead to decrease...
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.91.25.12086
更新日期:1994-12-06 00:00:00
abstract::The mapping of eye-specific, geniculocortical inputs to primary visual cortex (V1) is highly sensitive to the balance of correlated activity between the two eyes during a restricted postnatal critical period for ocular dominance plasticity. This critical period is likely to have amplified expression of genes and prote...
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.0710172105
更新日期:2008-07-08 00:00:00
abstract::Understanding the factors that shape macroevolutionary patterns in functional traits is a central goal of evolutionary biology. Alternative strategies of sexual reproduction (inbreeding vs. outcrossing) have divergent effects on population genetic structure and could thereby broadly influence trait evolution. However,...
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.1213867110
更新日期:2013-03-05 00:00:00
abstract::MurG is an essential glycosyltransferase that forms the glycosidic linkage between N-acetyl muramyl pentapeptide and N-acetyl glucosamine in the biosynthesis of the bacterial cell wall. This enzyme is a member of a major superfamily of NDP-glycosyltransferases for which no x-ray structures containing intact substrates...
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.0235749100
更新日期:2003-02-04 00:00:00
abstract::A compact, well-organized, and natural motif, stabilized by three disulfide bonds, is proposed as a basic scaffold for protein engineering. This motif contains 37 amino acids only and is formed by a short helix on one face and an antiparallel triple-stranded beta-sheet on the opposite face. It has been adopted by scor...
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.92.14.6404
更新日期:1995-07-03 00:00:00
abstract::The progesterone receptor (PGR) is a ligand-activated transcription factor with key roles in the regulation of female fertility. Much has been learned of the actions of PGR signaling through the use of pharmacologic inhibitors and genetic manipulation, using mouse mutagenesis. Characterization of rats with a null muta...
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.1601825113
更新日期:2016-04-12 00:00:00
abstract::HIV-1 infection in the brain induces neuronal apoptosis leading to HIV-associated dementia. To explore the underlying mechanism, we developed a murine model by using human peripheral blood mononuclear cell (PBMC)-transplanted nonobese diabetic (NOD)-severe combined immunodeficiency (SCID) (hu-PBMC-NOD-SCID) mice. Admi...
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.2628048100
更新日期:2003-03-04 00:00:00
abstract::Docosahexaenoic acid (DCHA), a major polyunsaturated acid component of fish lipid, is not a substrate for prostaglandin synthetase from ram seminal vesicles but is a strong competitive inhibitor (Ki, 0.36 microM) of the conversion by this enzyme of arachidonate (Km, 5.9 microM) to prostaglandins. In contrast, DCHA exh...
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.80.12.3581
更新日期:1983-06-01 00:00:00
abstract::Human IL-10 (hIL-10) modulates critical immune and inflammatory responses by way of interactions with its high- (IL-10R1) and low-affinity (IL-10R2) cell surface receptors. Human cytomegalovirus exploits the IL-10 signaling pathway by expressing a functional viral IL-10 homolog (cmvIL-10), which shares only 27% sequen...
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.152147499
更新日期:2002-07-09 00:00:00
abstract::We exploit the unusual genome organization of the ciliate cell to analyze the control of specific gene amplification during a nuclear differentiation process. Ciliates contain two types of nuclei within one cell, the macronucleus and the micronucleus; and after sexual reproduction a new macronucleus is formed from 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.1009284107
更新日期:2010-12-21 00:00:00
abstract::A mouse monoclonal antibody (7E6A5) of IgG isotype, reacting specifically with mucin-producing goblet cells of the human gastrointestinal tract, has been developed. 7E6A5 reacts by an ELISA with colonic protein eluted from a DEAE column. A screening by immunoperoxidase assay of 76 specimens from 19 different human tis...
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.84.10.3425
更新日期:1987-05-01 00:00:00
abstract::Rapamycin is a potent immunosuppressant that blocks the G1/S transition in antigen-activated T cells and in yeast. The similar effects of rapamycin in animal cells and yeast suggest that the biochemical steps affected by rapamycin are conserved. Using a two-hybrid system we isolated mammalian clones that interact with...
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.91.26.12574
更新日期:1994-12-20 00:00:00
abstract::The scaling of respiratory metabolism with body mass is one of the most pervasive phenomena in biology. Using a single allometric equation to characterize empirical scaling relationships and to evaluate alternative hypotheses about mechanisms has been controversial. We developed a method to directly measure respiratio...
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.0902554107
更新日期:2010-01-26 00:00:00
abstract::The 3' flanking region of the apolipoprotein B (apoB) gene contains a hypervariable region consisting of a variable number of tandemly repeated short A + T-rich DNA sequences (VNTRs). We present a general method that utilizes the polymerase chain reaction to rapidly and accurately type this and other VNTR loci. We use...
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.86.1.212
更新日期:1989-01-01 00:00:00
abstract::Behavioral and neural evidence reveal a prospective goal-directed decision process that relies on mental simulation of the environment, and a retrospective habitual process that caches returns previously garnered from available choices. Artificial systems combine the two by simulating the environment up to some depth ...
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.1609094113
更新日期:2016-11-08 00:00:00
abstract::In our 3D NOESY-[(1)H,(15)N,(1)H]-ZQ-TROSY experiment, the TROSY principle (transverse relaxation-optimized spectroscopy) is used in three-dimensional (3D) (15)N-resolved nuclear Overhauser enhancement spectroscopy (NOESY), which enables resonance assignments by sequential nuclear Overhauser effects and the collection...
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.96.17.9607
更新日期:1999-08-17 00:00:00