当前位置： SCI文献检索 > MOLECULAR AND CELLULAR BIOLOGY期刊下所有文献 > Analysis of the ligand-binding domain of human retinoic acid receptor alpha by site-directed mutagenesis.

Analysis of the ligand-binding domain of human retinoic acid receptor alpha by site-directed mutagenesis.

Abstract：

:Three subtypes of retinoic acid receptors (RAR), termed RAR alpha, RAR beta, and RAR gamma, have been described. They are composed of different structural domains, including distinct domains for DNA and ligand binding. RARs specifically bind all-trans-retinoic acid (RA), 9-cis-RA, and retinoid analogs. In this study, we examined the functional role of cysteine and arginine residues in the ligand-binding domain of hRAR alpha (hRAR alpha-LBD, amino acids 154 to 462). All conserved cysteine and arginine residues in this domain were mutated by site-directed mutagenesis, and the mutant proteins were characterized by blocking reactions, ligand-binding experiments, transactivation assays, and protease mapping. Changes of any cysteine residue of the hRAR alpha-LBD had no significant influence on the binding of all-trans RA or 9-cis RA. Interestingly, residue C-235 is specifically important in antagonist binding. With respect to arginine residues, only the two single mutations of R-276 and R-394 to alanine showed a dramatic decrease of agonist and antagonist binding whereas the R272A mutation showed only a slight effect. For all other arginine mutations, no differences in affinity were detectable. The two mutations R217A and R294A caused an increased binding efficiency for antagonists but no change in agonist binding. From these results, we can conclude that electrostatic interactions of retinoids with the RAR alpha-LBD play a significant role in ligand binding. In addition, antagonists show distinctly different requirements for efficient binding, which may contribute to their interference in the ligand-inducible transactivation function of RAR alpha.

journal_name

Mol Cell Biol

journal_title

Molecular and cellular biology

authors

Lamour FP,Lardelli P,Apfel CM

doi

10.1128/mcb.16.10.5386

subject

Has Abstract

pub_date

1996-10-01 00:00:00

pages

5386-92

issue

10

eissn

0270-7306

issn

1098-5549

journal_volume

16

pub_type

杂志文章

相关文献

MOLECULAR AND CELLULAR BIOLOGY文献大全
  • Saccharomyces cerevisiae Mob1p is required for cytokinesis and mitotic exit.

    abstract：:The Saccharomyces cerevisiae mitotic exit network (MEN) is a conserved set of genes that mediate the transition from mitosis to G(1) by regulating mitotic cyclin degradation and the inactivation of cyclin-dependent kinase (CDK). Here, we demonstrate that, in addition to mitotic exit, S. cerevisiae MEN gene MOB1 is req...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.21.20.6972-6983.2001

    authors： Luca FC,Mody M,Kurischko C,Roof DM,Giddings TH,Winey M

    更新日期：2001-10-01 00:00:00

  • Heat shock transcription factor Hsf1 is involved in tumor progression via regulation of hypoxia-inducible factor 1 and RNA-binding protein HuR.

    abstract：:Previously we demonstrated that the heat shock transcription factor Hsf1 is indispensable for transformation of mammary epithelial cells by the Her2 oncogene. Since Hsf1 affects oncogene-induced senescence (OIS), these findings suggest that Hsf1 affects tumor initiation when OIS plays a role. Indeed, here we report th...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.05921-11

    authors： Gabai VL,Meng L,Kim G,Mills TA,Benjamin IJ,Sherman MY

    更新日期：2012-03-01 00:00:00

  • Rgt1p of Saccharomyces cerevisiae, a key regulator of glucose-induced genes, is both an activator and a repressor of transcription.

    abstract：:The RGT1 gene of Saccharomyces cerevisiae plays a central role in the glucose-induced expression of hexose transporter (HXT) genes. Genetic evidence suggests that it encodes a repressor of the HXT genes whose function is inhibited by glucose. Here, we report the isolation of RGT1 and demonstrate that it encodes a bifu...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.16.11.6419

    authors： Ozcan S,Leong T,Johnston M

    更新日期：1996-11-01 00:00:00

  • Identification and partial characterization of an extracellular acid phosphatase activity of Leishmania donovani promastigotes.

    abstract：:An extracellular acid phosphatase was detected in the growth media of Leishmania donovani promastigotes. The enzyme was released at all stages of the growth cycle and in amounts which accounted for 90% of the total amount of this enzyme in the culture. The exoenzyme exhibited a pH optimum of 4.5 to 5.0 and was active ...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.2.1.76

    authors： Gottlieb M,Dwyer DM

    更新日期：1982-01-01 00:00:00

  • Expression of the Aplysia californica rho gene in Escherichia coli: purification and characterization of its encoded p21 product.

    abstract：:A new family of highly conserved genes, designated rho, has recently been isolated and characterized (P. Madaule and R. Axel, Cell 41:31-40, 1985). These genes have been found in Saccharomyces cerevisiae, Drosophila melanogaster, rats, and humans, and their 21,000-dalton products are highly homologous. The rho p21 pro...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.7.10.3620

    authors： Anderson PS,Lacal JC

    更新日期：1987-10-01 00:00:00

  • Calcineurin Broadly Regulates the Initiation of Skeletal Muscle-Specific Gene Expression by Binding Target Promoters and Facilitating the Interaction of the SWI/SNF Chromatin Remodeling Enzyme.

    abstract：:Calcineurin (Cn) is a calcium-activated serine/threonine protein phosphatase that is broadly implicated in diverse cellular processes, including the regulation of gene expression. During skeletal muscle differentiation, Cn activates the nuclear factor of activated T-cell (NFAT) transcription factor but also promotes d...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.00063-19

    authors： Witwicka H,Nogami J,Syed SA,Maehara K,Padilla-Benavides T,Ohkawa Y,Imbalzano AN

    更新日期：2019-09-11 00:00:00

  • Glypican 1 stimulates S phase entry and DNA replication in human glioma cells and normal astrocytes.

    abstract：:Malignant gliomas are highly lethal neoplasms with limited treatment options. We previously found that the heparan sulfate proteoglycan glypican 1 (GPC1) is universally and highly expressed in human gliomas. In this study, we investigated the biological activity of GPC1 expression in both human glioma cells and normal...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章,收录出版

    doi：10.1128/MCB.00238-13

    authors： Qiao D,Meyer K,Friedl A

    更新日期：2013-11-01 00:00:00

  • Recognition of RNA editing sites is directed by unique proteins in chloroplasts: biochemical identification of cis-acting elements and trans-acting factors involved in RNA editing in tobacco and pea chloroplasts.

    abstract：:RNA editing in higher-plant chloroplasts involves C-to-U conversions at specific sites. Although in vivo analyses have been performed, little is known about the biochemical aspects of chloroplast editing reactions. Here we improved our original in vitro system and devised a procedure for preparing active chloroplast e...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.22.19.6726-6734.2002

    authors： Miyamoto T,Obokata J,Sugiura M

    更新日期：2002-10-01 00:00:00

  • The 5' guanosine tracts of human telomerase RNA are recognized by the G-quadruplex binding domain of the RNA helicase DHX36 and function to increase RNA accumulation.

    abstract：:Telomerase promotes telomere maintenance by copying a template within its integral RNA subunit to elongate chromosome ends with new telomeric repeats. Motifs have been defined within the telomerase RNA that contribute to mature RNA accumulation, holoenzyme catalytic activity, or enzyme recruitment to telomeres. Here, ...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.01033-10

    authors： Sexton AN,Collins K

    更新日期：2011-02-01 00:00:00

  • Capped mRNA degradation intermediates accumulate in the yeast spb8-2 mutant.

    abstract：:mRNA in the yeast Saccharomyces cerevisiae is primarily degraded through a pathway that is stimulated by removal of the mRNA cap structure. Here we report that a mutation in the SPB8 (YJL124c) gene, initially identified as a suppressor mutation of a poly(A)-binding protein (PAB1) gene deletion, stabilizes the mRNA cap...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.18.9.5062

    authors： Boeck R,Lapeyre B,Brown CE,Sachs AB

    更新日期：1998-09-01 00:00:00

  • Imprinted Nesp55 influences behavioral reactivity to novel environments.

    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

    authors： Plagge A,Isles AR,Gordon E,Humby T,Dean W,Gritsch S,Fischer-Colbrie R,Wilkinson LS,Kelsey G

    更新日期：2005-04-01 00:00:00

  • Transcriptional regulation of a tumor promoter and mitogen-inducible gene in human lymphocytes.

    abstract：:Tumor-promoting phorbol esters affect a variety of cellular functions which may underlie tumor promotion. We isolated from human lymphocytes a cDNA clone whose gene is inducible by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate as well as by the T-cell mitogen phytohemagglutinin. Nuclear transcription experim...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.4.11.2540

    authors： Arya SK,Wong-Staal F,Gallo RC

    更新日期：1984-11-01 00:00:00

  • Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells.

    abstract：:The 54K cellular tumor antigen has been translated in vitro, using messenger ribonucleic acids from simian virus 40 (SV40)-transformed cells or 3T3 cells. The in vitro 54K product could be immunoprecipitated with SV40 tumor serum and had a peptide map that was similar, but not identical, to the in vivo product. The le...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.1.2.101

    authors： Oren M,Maltzman W,Levine AJ

    更新日期：1981-02-01 00:00:00

  • rme1 Mutation of Saccharomyces cerevisiae: map position and bypass of mating type locus control of sporulation.

    abstract：:Sporulation in Saccharomyces cerevisiae normally occurs only in MATa/MAT alpha diploids. We show that mutations in RME1 bypassed the requirements for both a and alpha mating type information in sporulation and therefore allowed MATa/MATa and MAT alpha/MAT alpha diploids to sporulate. RME1 was located on chromosome VII...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.1.10.958

    authors： Rine J,Sprague GF Jr,Herskowitz I

    更新日期：1981-10-01 00:00:00

  • Site-directed perturbation of protein kinase C- integrin interaction blocks carcinoma cell chemotaxis.

    abstract：:Polarized cell movement is an essential requisite for cancer metastasis; thus, interference with the tumor cell motility machinery would significantly modify its metastatic behavior. Protein kinase C alpha (PKC alpha) has been implicated in the promotion of a migratory cell phenotype. We report that the phorbol ester-...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.22.16.5897-5911.2002

    authors： Parsons M,Keppler MD,Kline A,Messent A,Humphries MJ,Gilchrist R,Hart IR,Quittau-Prevostel C,Hughes WE,Parker PJ,Ng T

    更新日期：2002-08-01 00:00:00

  • Target cell death triggered by cytotoxic T lymphocytes: a target cell mutant distinguishes passive pore formation and active cell suicide mechanisms.

    abstract：:The role of the target cell in its own death mediated by cytotoxic T lymphocytes (CTL) has been controversial. The ability of the pore-forming granule components of CTL to induce target cell death directly has been taken to suggest an essentially passive role for the target. This view of CTL-mediated killing ascribes ...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.14.1.427

    authors： Ucker DS,Wilson JD,Hebshi LD

    更新日期：1994-01-01 00:00:00

  • A novel intron element operates posttranscriptionally To regulate human N-myc expression.

    abstract：:Precisely regulated expression of oncogenes and tumor suppressor genes is essential for normal development, and deregulated expression can lead to cancer. The human N-myc gene normally is expressed in only a subset of fetal epithelial tissues, and its expression is extinguished in all adult tissues except transiently ...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.19.1.155

    authors： Sivak LE,Pont-Kingdon G,Le K,Mayr G,Tai KF,Stevens BT,Carroll WL

    更新日期：1999-01-01 00:00:00

  • Human MDM2 isoforms translated differentially on constitutive versus p53-regulated transcripts have distinct functions in the p53/MDM2 and TSG101/MDM2 feedback control loops.

    abstract：:Proteins encoded by the mdm2 gene, which has a pivotal role in the regulation of growth and differentiation, exist principally in human and murine cells as two isoforms that migrate in gels as 75-kDa and 90-kDa proteins. There is limited understanding of the respective biological roles of these isoforms, their molecul...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.00235-06

    authors： Cheng TH,Cohen SN

    更新日期：2007-01-01 00:00:00

  • Identification of single-stranded-DNA-binding proteins that interact with muscle gene elements.

    abstract：:A sequence-specific DNA-binding protein from skeletal-muscle extracts that binds to probes of three muscle gene DNA elements is identified. This protein, referred to as muscle factor 3, forms the predominant nucleoprotein complex with the MCAT gene sequence motif in an electrophoretic mobility shift assay. This protei...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.11.4.1944

    authors： Santoro IM,Yi TM,Walsh K

    更新日期：1991-04-01 00:00:00

  • NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release.

    abstract：:Muscle wasting (cachexia) is a consequence of chronic diseases, such as cancer, and is associated with degradation of muscle proteins such as MyoD. The cytokines tumor necrosis factor alpha and gamma interferon induce muscle degeneration by activating the transcription factor NF-kappaB and its target genes. Here, we s...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.25.15.6533-6545.2005

    authors： Di Marco S,Mazroui R,Dallaire P,Chittur S,Tenenbaum SA,Radzioch D,Marette A,Gallouzi IE

    更新日期：2005-08-01 00:00:00

  • The N Termini of TAR DNA-Binding Protein 43 (TDP43) C-Terminal Fragments Influence Degradation, Aggregation Propensity, and Morphology.

    abstract：:Fragments of the TAR DNA-binding protein 43 (TDP43) are major components of intracellular aggregates associated with amyotrophic lateral sclerosis and frontotemporal dementia. A variety of C-terminal fragments (CTFs) exist, with distinct N termini; however, little is known regarding their differences in metabolism and...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.00243-18

    authors： Kasu YAT,Alemu S,Lamari A,Loew N,Brower CS

    更新日期：2018-09-14 00:00:00

  • Immunosuppression by N-methyl-D-aspartate receptor antagonists is mediated through inhibition of Kv1.3 and KCa3.1 channels in T cells.

    abstract：:N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that play an important role in neuronal development, plasticity, and excitotoxicity. NMDAR antagonists are neuroprotective in animal models of neuronal diseases, and the NMDAR open-channel blocker memantine is used to treat Alzheimer's disease. In v...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.01273-13

    authors： Kahlfuß S,Simma N,Mankiewicz J,Bose T,Lowinus T,Klein-Hessling S,Sprengel R,Schraven B,Heine M,Bommhardt U

    更新日期：2014-03-01 00:00:00

  • Downstream 28S gene sequences on the RNA template affect the choice of primer and the accuracy of initiation by the R2 reverse transcriptase.

    abstract：:R2 non-long terminal repeat retrotransposable elements insert at a unique site in the 28S rRNA genes of insects. The protein encoded by the single open reading frame of R2 is capable of conducting the initial steps of its integration in vitro. The protein nicks the noncoding strand of the 28S target DNA (the strand wh...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.16.9.4726

    authors： Luan DD,Eickbush TH

    更新日期：1996-09-01 00:00:00

  • GAGA factor isoforms have distinct but overlapping functions in vivo.

    abstract：:The Drosophila melanogaster GAGA factor (encoded by the Trithorax-like [Trl] gene) is required for correct chromatin architecture at diverse chromosomal sites. The Trl gene encodes two alternatively spliced isoforms of the GAGA factor (GAGA-519 and GAGA-581) that are identical except for the length and sequence of the...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.21.24.8565-8574.2001

    authors： Greenberg AJ,Schedl P

    更新日期：2001-12-01 00:00:00

  • DNA-mediated transfer of human melanoma cell surface glycoprotein gp130: identification of transfectants by erythrocyte rosetting.

    abstract：:DNA sequences encoding a human melanoma membrane-bound sialoglycoprotein of 130,000 molecular weight (gp130) were introduced into a clonal derivative of mouse B-16 melanoma cells with the selectable neomycin resistance gene (aminoglycoside phosphotransferase). Mouse transfectants were identified by a rapid and precise...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.5.4.692

    authors： Albino AP,Graf LH Jr,Kantor RR,McLean W,Silagi S,Old LJ

    更新日期：1985-04-01 00:00:00

  • Transcription of the HS2 enhancer toward a cis-linked gene is independent of the orientation, position, and distance of the enhancer relative to the gene.

    abstract：:The locus control region (LCR) regulates transcription of the downstream beta-like globin genes 10 to 50 kb away. Among hypersensitive sites HS4, -3, -2, and -1, which define the LCR in erythroid cells, HS2 possesses prominent enhancer function. The mechanism by which the HS2 enhancer and other functional components o...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.17.7.3955

    authors： Kong S,Bohl D,Li C,Tuan D

    更新日期：1997-07-01 00:00:00

  • Regulation of chimeric phosphoenolpyruvate carboxykinase genes by the trans-dominant locus TSE1.

    abstract：:Extinction of phosphoenolpyruvate carboxykinase (PCK) gene expression in hepatoma x fibroblast hybrids is mediated by a trans-acting genetic locus designated tissue-specific extinguisher 1 (TSE1). To identify PCK gene sequences required for extinction, hepatoma transfectants expressing PCK-thymidine kinase (TK) chimer...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.10.6.2660

    authors： Thayer MJ,Lugo TG,Leach RJ,Fournier RE

    更新日期：1990-06-01 00:00:00

  • ATP binding by monarch-1/NLRP12 is critical for its inhibitory function.

    abstract：:The recently discovered nucleotide binding domain-leucine rich repeat (NLR) gene family is conserved from plants to mammals, and several members are associated with human autoinflammatory or immunodeficiency disorders. This family is defined by a central nucleotide binding domain that contains the highly conserved Wal...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.01468-07

    authors： Ye Z,Lich JD,Moore CB,Duncan JA,Williams KL,Ting JP

    更新日期：2008-03-01 00:00:00

  • Overproduction of Rb protein after the G1/S boundary causes G2 arrest.

    abstract：:The Rb protein is known to exert its activity at decision points in the G1 phase of the cell cycle. To investigate whether it may also play some role(s) at later points in the cell cycle, we used a system of rapid inducible gene amplification to conditionally overexpress Rb protein during G2 phase. A cell line express...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/mcb.13.11.6640

    authors： Karantza V,Maroo A,Fay D,Sedivy JM

    更新日期：1993-11-01 00:00:00

  • Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT.

    abstract：:SLP-76 is an adapter protein required for T-cell receptor (TCR) signaling. In particular, TCR-induced tyrosine phosphorylation and activation of phospholipase C-gamma1 (PLC-gamma1), and the resultant TCR-inducible gene expression, depend on SLP-76. Nonetheless, the mechanisms by which SLP-76 mediates PLC-gamma1 activa...

    journal_title：Molecular and cellular biology

    pub_type： 杂志文章

    doi：10.1128/MCB.21.13.4208-4218.2001

    authors： Yablonski D,Kadlecek T,Weiss A

    更新日期：2001-07-01 00:00:00