Abstract:
:In response to hypoxia the hypoxia-inducible factor-1 (HIF-1) mediates transcriptional activation of a network of genes encoding erythropoietin, vascular endothelial growth factor, and several glycolytic enzymes. HIF-1 consists of a heterodimer of two basic helix-loop-helix PAS (Per/Arnt/Sim) proteins, HIF-1alpha and Arnt. HIF-1alpha and Arnt mRNAs are constitutively expressed and were not altered upon exposure of HeLa or HepG2 cells to hypoxia, suggesting that the activity of the HIF-1alpha-Arnt complex may be regulated by some as yet unknown posttranscriptional mechanism. In support of this model, we demonstrate here that Arnt protein levels were not increased under conditions that induce an hypoxic response in HeLa and HepG2 cells. However, under identical conditions, HIF-1alpha protein levels were rapidly and dramatically up-regulated, as assessed by immunoblot analysis. In addition, HIF-1alpha acquired a new conformational state upon dimerization with Arnt, rendering HIF-1alpha more resistant to proteolytic digestion in vitro. Dimerization as such was not sufficient to elicit the conformational change in HIF-1alpha, since truncated forms of Arnt that are capable of dimerizing with HIF-1alpha did not induce this effect. Moreover, the high affinity DNA binding form of the HIF-1alpha-Arnt complex was only generated by forms of Arnt capable of eliciting the allosteric change in conformation. In conclusion, the combination of enhanced protein levels and allosteric change by dimerization defines a novel mechanism for modulation of transcription factor activity.
journal_name
Proc Natl Acad Sci U S Aauthors
Kallio PJ,Pongratz I,Gradin K,McGuire J,Poellinger Ldoi
10.1073/pnas.94.11.5667subject
Has Abstractpub_date
1997-05-27 00:00:00pages
5667-72issue
11eissn
0027-8424issn
1091-6490journal_volume
94pub_type
杂志文章abstract::An electron microscopic study of somatic hybrids resulting from a cross between hamster melanoma cells harboring R-type particles and mouse fibroblasts harboring intracisternal A-type and (mostly) immature C-type particles was performed. The major findings are: (a) hybrid cells that retain a large fraction of both ham...
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.71.11.4575
更新日期:1974-11-01 00:00:00
abstract::The evolutionary transition from single cells toward multicellular forms of life represents one of the major transitions in the evolution of complex organisms. In this transition, single autonomously reproducing cells became parts of larger reproducing entities that eventually constituted a new unit of selection. 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.0335420100
更新日期:2003-02-04 00:00:00
abstract::Incubation of physiological concentrations of 125I-labeled insulin with liver membranes in the presence of anti-insulin IgG results in a 7- to 15-fold increase in the specific binding of the hormone. The low-affinity/high-capacity binding sites are replaced by an apparently homogeneous class of high-affinity sites, 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.76.6.2720
更新日期:1979-06-01 00:00:00
abstract::Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embry...
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.1916034117
更新日期:2020-03-03 00:00:00
abstract::The Cdc6 protein is essential for the assembly of pre-replicative complexes (pre-RCs) at origins of DNA replication in the budding yeast Saccharomyces cerevisiae. This reaction is blocked in vivo by the cyclin-dependent kinase Cdc28p, together with its regulatory subunits, the B type cyclins that are present throughou...
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.94.11.5611
更新日期:1997-05-27 00:00:00
abstract::As the rate and magnitude of climate change accelerate, understanding the consequences becomes increasingly important. Species distribution models (SDMs) based on current ecological niche constraints are used to project future species distributions. These models contain assumptions that add to the uncertainty in model...
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.0901639106
更新日期:2009-11-17 00:00:00
abstract::The neotropical Heliconius butterflies are famous examples of Müllerian mimicry, due to the diverse array of shared, brightly colored wing patterns that advertise the butterflies' unpalatability. The parallel geographical variation in these patterns within several widespread species has been invoked to support the con...
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.91.14.6491
更新日期:1994-07-05 00:00:00
abstract::We propose that protein translocation across membranes is driven by biased random thermal motion. This "Brownian ratchet" mechanism depends on chemical asymmetries between the cis and trans sides of the membrane. Several mechanisms could contribute to rectifying the thermal motion of the protein, such as binding and 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.89.9.3770
更新日期:1992-05-01 00:00:00
abstract::mTOR is an evolutionarily conserved kinase that plays a critical role in sensing and responding to environmental determinants. Recent studies have shown that fine-tuning of the activity of mTOR complexes contributes to organogenesis and tumorigenesis. Although rapamycin, an allosteric mTOR inhibitor, is an effective i...
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.1320265111
更新日期:2014-03-11 00:00:00
abstract::Tumor hypoxia and the hypoxia-inducible factors (HIFs) play a central role in the development of cancer. To study the relationship between tumor growth, tumor hypoxia, the stabilization of HIF-1alpha, and HIF transcriptional activity, we have established an in vivo imaging tool that allows longitudinal and noninvasive...
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.0901194106
更新日期:2009-08-18 00:00:00
abstract::Most guanine nucleotide binding protein (G protein)-coupled receptors have a conserved cysteine in the C-terminal cytoplasmic tail near the seventh transmembrane spanning region. This cysteine is known to be palmitoylated in rhodopsin, the beta 2-adrenergic receptor (beta 2AR) and the alpha 2A-adrenergic receptor (alp...
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.91.23.11178
更新日期:1994-11-08 00:00:00
abstract::The human immunodeficiency virus (HIV) genetic determinant(s) responsible for tropism in human T cells or macrophages are not well defined. We studied the role of the HIV type 2 (HIV-2) nef and vpr genes in viral tropism. HIV-2 mutants, lacking either vpr or nef genes, or both vpr and nef, were obtained by site-specif...
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.87.20.8080
更新日期:1990-10-01 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::Allergies are highly prevalent, and allergic responses can be triggered even in the absence of allergens due to Pavlovian conditioning to a specific cue. Here we show in humans suffering from allergic rhinitis that merely reencountering the environmental context in which an allergen was administered a week earlier is ...
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.1920564117
更新日期:2020-05-19 00:00:00
abstract::The somatostatin receptor subtype 2 (sst2) behaves as a tumor suppressor when expressed and stimulated by its ligand somatostatin in pancreatic cancer. We reveal a mechanism underlying oncosuppressive action of sst2, whereby this inhibitory receptor upregulates the expression of the secreted angioinhibitory factor thr...
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.0908674106
更新日期:2009-10-20 00:00:00
abstract::In adipocytes, adenylate cyclase is positively regulated by beta-adrenergic agents and negatively regulated by adenosine. Incubation of adipocytes with adenosine deaminase relieves the inhibition of adenylate cyclase by destroying the adenosine that the cells release into the medium. When adipocytes are incubated 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.82.6.1614
更新日期:1985-03-01 00:00:00
abstract::For several decades, the iron-based Fenton-like catalysis has been believed to be mediated by hydroxyl radicals or high-valent iron-oxo species, while only sporadic evidence supported the generation of singlet oxygen (1O2) in the Haber-Weiss cycle. Herein, we report an unprecedented singlet oxygen mediated Fenton-like...
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.1819382116
更新日期:2019-04-02 00:00:00
abstract::Magnetic ground states in solids often arise as a result of a delicate balance between competing factors. One currently active area of research in magnetic materials involves compounds in which long-range magnetic ordering at low temperatures is frustrated by the geometry of the crystalline lattice, a situation known ...
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.0832394100
更新日期:2003-07-08 00:00:00
abstract::The outcome of exposure to infectious microbes or their toxins is influenced by both microbial and host genes. Some host genes encode defense mechanisms, whereas others assist pathogen functions. Genomic analyses have associated host gene mutations with altered infectious disease susceptibility, but evidence for causa...
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.1121006109
更新日期:2012-02-21 00:00:00
abstract::Representations of the (infinite) canonical anticommutation relations and the associated operator algebra, the fermion algebra, are studied. A "coupling constant" (in (0,1]) is defined for primary states of "finite type" of that algebra. Primary, faithful states of finite type with arbitrary coupling are constructed 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.95.23.13392
更新日期:1998-11-10 00:00:00
abstract::VIP21/caveolin is localized to both caveolae and apical transport vesicles and presumably cycles between the cell surface and the Golgi complex. We have studied the lipid interactions of this protein by reconstituting Escherichia coli-expressed VIP21/caveolin into liposomes. Surprisingly, the protein reconstituted onl...
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.92.22.10339
更新日期:1995-10-24 00:00:00
abstract::A descriptive medium for the presentation of protein structure has been developed and used to evaluate the structure of the active site of bovine trypsin (EC 3.4.21.4). This technique, involving advanced computer graphics technology, permits the facile display of a representation of the molecular surface of proteins o...
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.75.11.5409
更新日期:1978-11-01 00:00:00
abstract::Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid gastrointestinal regulatory peptide that stimulates insulin secretion from pancreatic beta cells in the presence of glucose. Approximately 7.8 x 10(5) recombinant clones of a neonatal rat intestinal cDNA library were screened by using plaque hybridizati...
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.90.5.1992
更新日期:1993-03-01 00:00:00
abstract::Impaired magnesium reabsorption in patients with TRPM6 gene mutations stresses an important role of TRPM6 (melastatin-related TRP cation channel) in epithelial magnesium transport. While attempting to isolate full-length TRPM6, we found that the human TRPM6 gene encodes multiple mRNA isoforms. Full-length TRPM6 varian...
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.0305252101
更新日期:2004-03-02 00:00:00
abstract::The solar system formed from interstellar dust and gas in a molecular cloud. Astronomical observations show that typical interstellar dust consists of amorphous (a-) silicate and organic carbon. Bona fide physical samples for laboratory studies would yield unprecedented insight about solar system formation, but they 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.1720167115
更新日期:2018-06-26 00:00:00
abstract::Four cell types from Vicia faba Linnaeus "Long Pod" leaflets were assayed for three enzymes unique to the photosynthetic carbon reduction pathway. The enzymes were ribulosebisphosphate carboxylase [3-phospho-D-glycerate carboxy-lyase (dimerizing), EC 4.1.1.39], phosphoribulokinase (ATP:D-ribulose-5-phosphate 1-phospho...
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.76.12.6371
更新日期:1979-12-01 00:00:00
abstract::Trisomy is a genetic abnormality of considerable medical importance. The most familiar example is trisomy 21, which causes Down Syndrome [Cummings, M. R. (1988) Human Heredity: Principles and Issues (West Publishing Company, New York)]. In a classic paper, Axelrod and Hamilton [Axelrod, R. & Hamilton, W. D. (1981) Sci...
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.95.5.2361
更新日期:1998-03-03 00:00:00
abstract::A densely packed granular system is an example of an out-of-equilibrium system in the jammed state. It has been a longstanding problem to determine whether this class of systems can be described by concepts arising from equilibrium statistical mechanics, such as an effective temperature and compactivity. The measureme...
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.0409911102
更新日期:2005-02-15 00:00:00
abstract::MicroRNAs (miRNAs) are 18- to 24-nt RNA molecules that regulate messenger RNAs (mRNAs). Posttranscriptional mechanisms regulate miRNA abundance during development as well as in cancer cells where miRNAs frequently exhibit dysregulated expression. The molecular mechanisms that govern the global efficiency of miRNA biog...
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.0811523106
更新日期:2009-04-28 00:00:00
abstract::The steroidogenic acute regulatory protein (StAR) increases the movement of cholesterol from the outer to the inner membrane of adrenal and gonadal mitochondria, thus providing the substrate for steroid hormone biosynthesis. Deletion of 62 amino-terminal aa produces a cytoplasmic form of StAR (N-62 StAR) that lacks th...
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.96.13.7250
更新日期:1999-06-22 00:00:00