Abstract:
:Posttranscriptional regulation is important for tumor necrosis factor alpha (TNF-alpha) expression in monocytes and macrophages, and an AU-rich element (ARE) in the 3' untranslated region (UTR) of TNF-alpha mRNA is implicated in control of its translation and mRNA stability. Regulation of mRNA turnover is thought to be mediated by trans-acting proteins, which bind the ARE and stabilize or destabilize the transcript. However, with the exception of the destabilizing factor tristetraprolin, the identity and function of the proteins binding the TNF-alpha mRNA ARE have not been established. To identify other proteins involved in the posttranscriptional control of TNF-alpha, the subcellular location of TNF-alpha mRNA was determined in the macrophage-like cell line RAW 264.7. TNF-alpha mRNA was located in the pellet following centrifugation of cytoplasm at 100,000 x g (P100 fraction). This fraction also contained proteins which formed two distinct ARE-specific complexes with the TNF-alpha mRNA 3' UTR in electrophoretic mobility shift assays (EMSAs). A protein present in these two complexes was purified and identified by peptide mass mapping and tandem mass spectrometry as HuR. In EMSAs both complexes were supershifted by an anti-HuR antibody, while Western blotting also demonstrated the presence of HuR in the P100 extract. A HeLa cell tetracycline-regulated reporter system was used to determine the effect of HuR on mRNA stability. In this system, overexpression of HuR resulted in stabilization of an otherwise unstable reporter-mRNA containing the TNF-alpha ARE. These results demonstrate that the TNF-alpha ARE is a target of the mRNA-stabilizing factor HuR.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Dean JL,Wait R,Mahtani KR,Sully G,Clark AR,Saklatvala Jdoi
10.1128/MCB.21.3.721-730.2001subject
Has Abstractpub_date
2001-02-01 00:00:00pages
721-30issue
3eissn
0270-7306issn
1098-5549journal_volume
21pub_type
杂志文章abstract::Genomic imprinting results in parent-of-origin-dependent monoallelic expression of selected genes. Although their importance in development and physiology is recognized, few imprinted genes have been investigated for their effects on brain function. Gnas is a complex imprinted locus whose gene products are involved in...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.8.3019-3026.2005
更新日期:2005-04-01 00:00:00
abstract::Mitogen-activated protein (MAP) kinase phosphatase 1 (MKP-1) has been shown to play a critical role in mediating the feedback control of MAP kinase cascades in a variety of cellular processes, including proliferation and stress responsiveness. Although MKP-1 expression is induced by a broad array of extracellular stim...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.23.8213-8224.2001
更新日期:2001-12-01 00:00:00
abstract::Phosphatidylinositol (PI) 3-kinase is a cytoplasmic signaling molecule recruited to the membrane by activated growth factor receptors. The p85 subunit of PI 3-kinase links the catalytic p110 subunit to activated growth factor receptors and is required for enzymatic activity of p110. In this report, we describe the eff...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.16.8.4117
更新日期:1996-08-01 00:00:00
abstract::Small nucleolar RNAs (snoRNAs) orchestrate the modification and cleavage of pre-rRNA and are essential for ribosome biogenesis. Recent data suggest that after nucleoplasmic synthesis, snoRNAs transiently localize to the Cajal body (in plant and animal cells) or the homologous nucleolar body (in budding yeast) for matu...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01115-07
更新日期:2008-06-01 00:00:00
abstract::Adenovirus E1A pre-mRNA was used as a model to examine alternative 5' splice site selection during in vitro splicing reactions. Strong preference for the downstream 13S 5' splice site over the upstream 12S or 9S 5' splice sites was observed. However, the 12S 5' splice site was used efficiently when a mutant pre-mRNA l...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.12.5945
更新日期:1991-12-01 00:00:00
abstract::Fibroblasts transformed by Fos oncogenes display increased expression of a number of genes implicated in tumor cell invasion and metastasis. In contrast to normal 208F rat fibroblasts, Fos-transformed 208F fibroblasts are growth factor independent for invasion. We demonstrate that invasion of v-Fos- or epidermal growt...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.17.2.963
更新日期:1997-02-01 00:00:00
abstract::A cDNA encoding a novel Krüppel-type zinc finger protein, FKLF, was cloned from fetal globin-expressing human fetal erythroid cells. The deduced polypeptide sequence composed of 512 amino acids revealed that, like Sp1 and EKLF, FKLF has three contiguous zinc fingers at the near carboxyl-terminal end. A long amino-term...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.5.3571
更新日期:1999-05-01 00:00:00
abstract::Analysis of a T-cell antigen receptor (TCR) alpha promoter from a variable gene segment (V) revealed a critical GT box element which is also found in upstream regions of several V alpha genes, TCR enhancer, and regulatory elements of other genes. This element is necessary for TCR gene expression and binds several prot...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.10.4251
更新日期:1992-10-01 00:00:00
abstract::The neuron-specific N1 exon of the mouse c-src transcript is normally skipped in nonneuronal cells. In this study, we examined the sequence requirements for the exclusion of this exon in nonneuronal HeLa cell nuclear extracts. We found that the repression of the N1 exon is mediated by specific intron sequences that fl...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.15.11.6377
更新日期:1995-11-01 00:00:00
abstract::Cells of Candida albicans WO-1 spontaneously switch between a white and opaque CFU, and this phase transition involves a dramatic change in cellular phenotype. By using a differential hybridization screen, an opaque-specific cDNA, Op1a, which represents the transcript of a gene regulated by switching, has been isolate...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.12.7.2997
更新日期:1992-07-01 00:00:00
abstract::To clarify carbon source-dependent control of the glycolytic pathway in the yeast Saccharomyces cerevisiae, we have initiated a study of transcriptional regulation of the pyruvate kinase gene (PYK). By deletion analysis of the 5'-noncoding region of the PYK gene, we have identified an upstream activating sequence (UAS...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.2.442
更新日期:1989-02-01 00:00:00
abstract::Erythroid Krüppel-like factor (EKLF [KLF1]) is a transcriptional regulator that plays a critical role within a specific subset of hematopoietic cells, particularly in the erythroid lineage and its immediate precursor, the megakaryocyte-erythroid progenitor (MEP). We find that EKLF is posttranslationally modified by su...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00589-07
更新日期:2007-12-01 00:00:00
abstract::Mitoferrin 1 (Mfrn1; Slc25a37) and mitoferrin 2 (Mfrn2; Slc25a28) function as essential mitochondrial iron importers for heme and Fe/S cluster biogenesis. A genetic deficiency of Mfrn1 results in a profound hypochromic anemia in vertebrate species. To map the cis-regulatory modules (CRMs) that control expression of th...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01010-10
更新日期:2011-04-01 00:00:00
abstract::Allelic forms of DRG1/AFG2 confer resistance to the drug diazaborine, an inhibitor of ribosome biogenesis in Saccharomyces cerevisiae. Our results show that the AAA-ATPase Drg1 is essential for 60S maturation and associates with 60S precursor particles in the cytoplasm. Functional inactivation of Drg1 leads to an incr...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00668-07
更新日期:2007-10-01 00:00:00
abstract::Endonuclease decay of nonsense-containing beta-globin mRNA in erythroid cells generates 5'-truncated products that were reported previously to have a cap or caplike structure. We confirmed that this 5' modification is indistinguishable from the cap on full-length mRNA, and Western blotting, immunoprecipitation, and ac...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01325-08
更新日期:2009-04-01 00:00:00
abstract::Protein ubiquitination provides an efficient and reversible mechanism to regulate cell cycle progression and checkpoint control. Numerous regulatory proteins direct the addition of ubiquitin to lysine residues on target proteins, and these are countered by an army of deubiquitinating enzymes (DUBs). BRCA1-associated p...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01517-08
更新日期:2009-04-01 00:00:00
abstract::We have functionally tested derivatives of a muscle-specific Drosophila melanogaster actin gene in which 5'-flanking sequences have been deleted or rearranged. From our results we conclude that approximately 1,000 nucleotides of 5'-flanking sequence are required for wild-type levels of mRNA accumulation during flight ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.10.3388
更新日期:1986-10-01 00:00:00
abstract::Growth factors and cyclic AMP (cAMP) are known to activate distinct intracellular signaling pathways. Fibroblast growth factor (FGF) activates ras-dependent kinase cascades, resulting in the activation of MAP kinases, whereas cAMP activates protein kinase A. In this study, we report that growth factors and cAMP act sy...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.14.11.7546
更新日期:1994-11-01 00:00:00
abstract::We investigated the role of RNA polymerase II (pol II) carboxy-terminal domain (CTD) phosphorylation in pre-mRNA processing coupled and uncoupled from transcription in Xenopus oocytes. Inhibition of CTD phosphorylation by the kinase inhibitors 5,6-dichloro-1beta-D-ribofuranosyl-benzimidazole and H8 blocked transcripti...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.24.20.8963-8969.2004
更新日期:2004-10-01 00:00:00
abstract::We have identified stable transcripts from the so-called nontranscribed spacer region (NTS) of the nuclear ribosomal DNA repeat in certain respiration-deficient strains of Saccharomyces cerevisiae. These RNAs, which are transcribed from the same strand as is the 37S rRNA precursor, are 500 to 800 nucleotides long and ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.5.1897
更新日期:1989-05-01 00:00:00
abstract::To examine the role of simian virus 40 (SV40) large T and small t antigens in tumorigenesis in animals, we generated transgenic mice which expressed either both the SV40 large T and small t antigens or the SV40 large T antigen alone under the control of the mouse mammary tumor virus long terminal repeat. The mouse mam...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.8.8.3382
更新日期:1988-08-01 00:00:00
abstract::The Csk tyrosine kinase negatively regulates the Src family kinases Lck and Fyn in T cells. Engagement of the T-cell antigen receptor results in a removal of Csk from the lipid raft-associated transmembrane protein PAG/Cbp. Instead, Csk becomes associated with an approximately 72-kDa tyrosine-phosphorylated protein, w...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.6.2227-2241.2005
更新日期:2005-03-01 00:00:00
abstract::Telomerase is a ribonucleoprotein enzyme that adds repetitive sequences to the ends of linear chromosomes, thereby counteracting nucleotide loss due to incomplete replication. A short region of the telomerase RNA subunit serves as template for nucleotide addition onto the telomere 3' end. Although Saccharomyces cerevi...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.21.7277-7286.2001
更新日期:2001-11-01 00:00:00
abstract::Sensory hair cells convert mechanical motion into chemical signals. Otoferlin, a six-C2 domain transmembrane protein linked to deafness in humans, is hypothesized to play a role in exocytosis at hair cell ribbon synapses. To date, however, otoferlin has been studied almost exclusively in mouse models, and no rescue ex...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01439-14
更新日期:2015-03-01 00:00:00
abstract::DHTKD1, a part of 2-ketoadipic acid dehydrogenase complex, is involved in lysine and tryptophan catabolism. Mutations in DHTKD1 block the metabolic pathway and cause 2-aminoadipic and 2-oxoadipic aciduria (AMOXAD), an autosomal recessive inborn metabolic disorder. In addition, a nonsense mutation in DHTKD1 that we ide...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.00085-18
更新日期:2018-06-14 00:00:00
abstract::The adenovirus EIa gene products activate transcription from the viral EIII and EIIaE promoters. We studied the mechanism of this stimulation by constructing a series of chimeric promoter recombinants containing the upstream regions of the EIII and EIIaE promoters linked to the TATA box-start-site regions of the viral...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.6.1.201
更新日期:1986-01-01 00:00:00
abstract::Unlike other eukaryotes, the protein-coding genes of Trypanosoma cruzi are arranged in large polycistronic gene clusters transcribed by polymerase II (Pol II). Thus, it is thought that trypanosomes rely solely on posttranscriptional processes to regulate gene expression. Here, we show that the glucosylated thymine DNA...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.01277-10
更新日期:2011-04-01 00:00:00
abstract::We have previously described an isolated kinetoplast system from Crithidia fasciculata capable of ATP-dependent replication of kinetoplast DNA minicircles (L. Birkenmeyer and D.S. Ray, J. Biol. Chem. 261: 2362-2368, 1986). We present here the identification of two new minicircle species observed in short pulse-labelin...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.9.1.169
更新日期:1989-01-01 00:00:00
abstract::We have investigated the in vivo and in vitro regulation of the human urokinase-type plasminogen activator (uPA) gene by interleukin-1 (IL-1) and analyzed the transcription factors and signalling pathways involved in the response of the -2.0-kb uPA enhancer to IL-1 induction and to tetradecanoyl phorbol acetate (TPA) ...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.19.9.6240
更新日期:1999-09-01 00:00:00
abstract::Caspases play important roles in apoptotic cell death and in some other functions, such as cytokine maturation, inflammation, or differentiation. We show here that the 5'-flanking region of the human CASP-2 gene contains three functional response elements for sterol regulatory element binding proteins (SREBPs), protei...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.25.21.9621-9631.2005
更新日期:2005-11-01 00:00:00