Hepatitis C virus nonstructural 5B protein regulates tumor necrosis factor alpha signaling through effects on cellular IkappaB kinase.


:Hepatitis C virus (HCV) NS5B protein is a membrane-associated phosphoprotein that possesses an RNA-dependent RNA polymerase activity. We recently reported that NS5A protein interacts with TRAF2 and modulates tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB and Jun N-terminal protein kinase (JNK). Since NS5A and NS5B are the essential components of the HCV replication complex, we examined whether NS5B could modulate TNF-alpha-induced NF-kappaB and JNK activation. In this study, we have demonstrated that TNF-alpha-induced NF-kappaB activation is inhibited by NS5B protein in HEK293 and hepatic cells. Furthermore, NS5B protein inhibited both TRAF2- and IKK-induced NF-kappaB activation. Using coimmunoprecipitation assays, we show that NS5B interacts with IKKalpha. Most importantly, NS5B protein in HCV subgenomic replicon cells interacted with endogenous IKKalpha, and then TNF-alpha-mediated IKKalpha kinase activation was significantly decreased by NS5B. Using in vitro kinase assay, we have further found that NS5B protein synergistically activated TNF-alpha-mediated JNK activity in HEK293 and hepatic cells. These data suggest that NS5B protein modulates TNF-alpha signaling pathways and may contribute to HCV pathogenesis.


Mol Cell Biol


Choi SH,Park KJ,Ahn BY,Jung G,Lai MM,Hwang SB




Has Abstract


2006-04-01 00:00:00














  • Many transcribed regions of the Onchocerca volvulus genome contain the spliced leader sequence of Caenorhabditis elegans.

    abstract::Genomic DNAs of the related parasitic nematodes Onchocerca volvulus and Dirofilariae immitis, and a cDNA library of O. volvulus, were examined for the presence of the 22-nucleotide spliced leader (SL) found at the 5' ends of 10 to 15% of the mRNAs in the free-living nematode Caenorhabditis elegans. As in C. elegans, g...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Zeng WL,Alarcon CM,Donelson JE

    更新日期:1990-06-01 00:00:00

  • Tim4- and MerTK-mediated engulfment of apoptotic cells by mouse resident peritoneal macrophages.

    abstract::Apoptotic cells are swiftly engulfed by macrophages to prevent the release of noxious materials from dying cells. Apoptotic cells expose phosphatidylserine (PtdSer) on their surface, and macrophages engulf them by recognizing PtdSer using specific receptors and opsonins. Here, we found that mouse resident peritoneal m...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Nishi C,Toda S,Segawa K,Nagata S

    更新日期:2014-04-01 00:00:00

  • Highly mutable sites for ICR-170-induced frameshift mutations are associated with potential DNA hairpin structures: studies with SUP4 and other Saccharomyces cerevisiae genes.

    abstract::The majority of the mutations induced by ICR-170 in both the CYC1 gene (J. F. Ernst et al. Genetics 111:233-241, 1985) and the HIS4 gene (L. Mathison and M. R. Culbertson, Mol. Cell. Biol. 5:2247-2256, 1985) of the yeast Saccharomyces cerevisiae were recently shown to be single G . C base-pair insertions at monotonous...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hampsey DM,Koski RA,Sherman F

    更新日期:1986-12-01 00:00:00

  • Negative regulation contributes to tissue specificity of the immunoglobulin heavy-chain enhancer.

    abstract::We have identified in and around the immunoglobulin heavy-chain enhancer two apparently distinct negative regulatory elements which repress immunoglobulin H enhancer, simian virus 40 enhancer, and heterologous promoter activity in fibroblasts but not in myeloma cells. We propose that in nonlymphoid cells, negative reg...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Imler JL,Lemaire C,Wasylyk C,Wasylyk B

    更新日期:1987-07-01 00:00:00

  • The CDK7-cycH-p36 complex of transcription factor IIH phosphorylates p53, enhancing its sequence-specific DNA binding activity in vitro.

    abstract::Phosphorylation is believed to be one of the mechanisms by which p53 becomes activated or stabilized in response to cellular stress. Previously, p53 was shown to interact with three components of transcription factor IIH (TFIIH): excision repair cross-complementing types 2 and 3 (ERCC2 and ERCC3) and p62. This communi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lu H,Fisher RP,Bailey P,Levine AJ

    更新日期:1997-10-01 00:00:00

  • Carcinogenic nickel silences gene expression by chromatin condensation and DNA methylation: a new model for epigenetic carcinogens.

    abstract::A transgenic gpt+ Chinese hamster cell line (G12) was found to be susceptible to carcinogenic nickel-induced inactivation of gpt expression without mutagenesis or deletion of the transgene. Many nickel-induced 6-thioguanine-resistant variants spontaneously reverted to actively express gpt, as indicated by both reversi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lee YW,Klein CB,Kargacin B,Salnikow K,Kitahara J,Dowjat K,Zhitkovich A,Christie NT,Costa M

    更新日期:1995-05-01 00:00:00

  • Matrix attachment regions are positioned near replication initiation sites, genes, and an interamplicon junction in the amplified dihydrofolate reductase domain of Chinese hamster ovary cells.

    abstract::Genomic DNA in higher eucaryotic cells is organized into a series of loops, each of which may be affixed at its base to the nuclear matrix via a specific matrix attachment region (MAR). In this report, we describe the distribution of MARs within the amplified dihydrofolate reductase (DHFR) domain (amplicon) in the met...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Dijkwel PA,Hamlin JL

    更新日期:1988-12-01 00:00:00

  • The bcl-3 proto-oncogene encodes a nuclear I kappa B-like molecule that preferentially interacts with NF-kappa B p50 and p52 in a phosphorylation-dependent manner.

    abstract::The product of the putative proto-oncogene bcl-3 is an I kappa B-like molecule with novel binding properties specific for a subset of the rel family of transcriptional regulators. In vitro, Bcl-3 protein specifically inhibited the DNA binding of both the homodimeric NF-kappa B p50 subunit and a closely related homolog...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Nolan GP,Fujita T,Bhatia K,Huppi C,Liou HC,Scott ML,Baltimore D

    更新日期:1993-06-01 00:00:00

  • Distinct subclasses of small GTPases interact with guanine nucleotide exchange factors in a similar manner.

    abstract::The Ras-related GTPases are small, 20- to 25-kDa proteins which cycle between an inactive GDP-bound form and an active GTP-bound state. The Ras superfamily includes the Ras, Rho, Ran, Arf, and Rab/YPT1 families, each of which controls distinct cellular functions. The crystal structures of Ras, Rac, Arf, and Ran reveal...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Day GJ,Mosteller RD,Broek D

    更新日期:1998-12-01 00:00:00

  • Methylation and rearrangement of mouse intracisternal a particle genes in development, aging, and myeloma.

    abstract::Sequences of DNA that hybridize on Southern blots with cloned intracisternal A-particle (IAP) sequences have been examined in genomic DNAs of neonatal mice, livers of adult mice (3, 6, 12, 18, 24, and 26 months old), and the solid myeloma tumor MOPC-315. The isoschizomers HpaII (CCGG or mCCGG) and MspI (CCGG or CmCGG)...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Mays-Hoopes LL,Brown A,Huang RC

    更新日期:1983-08-01 00:00:00

  • Natural and synthetic DNA elements with the CArG motif differ in expression and protein-binding properties.

    abstract::DNA elements with the CC(A/T)6GG, or CArG, motif occur in promoters that are under different regulatory controls. CArG elements from the skeletal actin, c-fos, and myogenin genes were tested for their abilities to confer tissue-specific expression on reporter genes when the individual elements were situated immediatel...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Santoro IM,Walsh K

    更新日期:1991-12-01 00:00:00

  • The amino-terminal region of Drosophila MSL1 contains basic, glycine-rich, and leucine zipper-like motifs that promote X chromosome binding, self-association, and MSL2 binding, respectively.

    abstract::In Drosophila melanogaster, X chromosome dosage compensation is achieved by doubling the transcription of most X-linked genes. The male-specific lethal (MSL) complex is required for this process and binds to hundreds of sites on the male X chromosome. The MSL1 protein is essential for X chromosome binding and serves a...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Li F,Parry DA,Scott MJ

    更新日期:2005-10-01 00:00:00

  • Hydrogen peroxide triggers nuclear export of telomerase reverse transcriptase via Src kinase family-dependent phosphorylation of tyrosine 707.

    abstract::The regulation of telomerase reverse transcriptase (TERT) plays an important role in the proliferative capacity and survival of cells. Here, we report that exogenously as well as endogenously induced oxidative stress leads to translocation of endogenous as well as overexpressed human TERT from the nucleus into the cyt...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Haendeler J,Hoffmann J,Brandes RP,Zeiher AM,Dimmeler S

    更新日期:2003-07-01 00:00:00

  • Transcription from the polyoma late promoter in cells stably transformed by chimeric plasmids.

    abstract::We have examined the expression of chimeric plasmids containing coding sequences for the herpes simplex virus thymidine kinase (tk) gene or the Tn5 gene for neomycin resistance (neo) linked to the late promoter of polyoma DNA. Although polyoma late genes are generally not expressed in transformed cells containing only...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Kern FG,Basilico C

    更新日期:1985-04-01 00:00:00

  • Tsr4 Is a Cytoplasmic Chaperone for the Ribosomal Protein Rps2 in Saccharomyces cerevisiae.

    abstract::Eukaryotic ribosome biogenesis requires the action of approximately 200 trans-acting factors and the incorporation of 79 ribosomal proteins (RPs). The delivery of RPs to preribosomes is a major challenge for the cell because RPs are often highly basic and contain intrinsically disordered regions prone to nonspecific i...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Black JJ,Musalgaonkar S,Johnson AW

    更新日期:2019-08-12 00:00:00

  • Analysis of TFIIA function In vivo: evidence for a role in TATA-binding protein recruitment and gene-specific activation.

    abstract::Activation of transcription can occur by the facilitated recruitment of TFIID to promoters by gene-specific activators. To investigate the role of TFIIA in TFIID recruitment in vivo, we exploited a class of yeast TATA-binding protein (TBP) mutants that is activation and DNA binding defective. We found that co-overexpr...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Liu Q,Gabriel SE,Roinick KL,Ward RD,Arndt KM

    更新日期:1999-12-01 00:00:00

  • Cell-extracellular matrix interactions stimulate the AP-1 transcription factor in an integrin-linked kinase- and glycogen synthase kinase 3-dependent manner.

    abstract::Integrin-mediated interactions of cells with components of the extracellular matrix regulate cell survival, cell proliferation, cell differentiation, and cell migration. Some of these physiological responses are regulated via activation of transcription factors such as activator protein 1 (AP-1). Integrin-linked kinas...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Troussard AA,Tan C,Yoganathan TN,Dedhar S

    更新日期:1999-11-01 00:00:00

  • Hormonal induction of transfected genes depends on DNA topology.

    abstract::Plasmids containing the hormone regulatory element of mouse mammary tumor virus linked to the thymidine kinase promoter of herpes simplex virus and the reporter gene chloramphenicol acetyltransferase of Escherichia coli respond to glucocorticoids and progestins when transfected into appropriate cells. In the human mam...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Piña B,Haché RJ,Arnemann J,Chalepakis G,Slater EP,Beato M

    更新日期:1990-02-01 00:00:00

  • Inhibition of nuclear receptor signalling by poly(ADP-ribose) polymerase.

    abstract::Mammalian poly(ADP-ribose) polymerase (PARP) is a nuclear chromatin-associated protein with a molecular mass of 114 kDa that catalyzes the transfer of ADP-ribose units from NAD+ to nuclear proteins that are located within chromatin. We report here the identification of a novel property of PARP as a modulator of nuclea...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Miyamoto T,Kakizawa T,Hashizume K

    更新日期:1999-04-01 00:00:00

  • Alternative RNA editing produces a novel protein involved in mitochondrial DNA maintenance in trypanosomes.

    abstract::The mitochondrial genome of trypanosomes is composed of thousands of topologically interlocked circular DNA molecules that form the kinetoplast DNA (kDNA). Most genes encoded by the kDNA require a posttranscriptional modification process called RNA editing to form functional mRNAs. Here, we show that alternative editi...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Ochsenreiter T,Anderson S,Wood ZA,Hajduk SL

    更新日期:2008-09-01 00:00:00

  • The genome of Shope fibroma virus, a tumorigenic poxvirus, contains a growth factor gene with sequence similarity to those encoding epidermal growth factor and transforming growth factor alpha.

    abstract::Degenerate oligonucleotide probes corresponding to a highly conserved region common to epidermal growth factor, transforming growth factor alpha, and vaccinia growth factor were used to identify a novel growth factor gene in the Shope fibroma virus genome. Sequence analysis indicates that the Shope fibroma growth fact...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Chang W,Upton C,Hu SL,Purchio AF,McFadden G

    更新日期:1987-01-01 00:00:00

  • Structure of the bovine tau gene: alternatively spliced transcripts generate a protein family.

    abstract::Tau, a major class of microtubule-associated proteins, consists of a family of proteins that are heterogeneous in molecular weight. The presence of internal deletions in previously described cDNA clones for murine and bovine tau suggested that alternative splicing of transcripts could account for the protein size hete...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Himmler A

    更新日期:1989-04-01 00:00:00

  • Dominant negative mutants of transforming growth factor-beta 1 inhibit the secretion of different transforming growth factor-beta isoforms.

    abstract::Transforming growth factor-beta (TGF-beta) is a secreted polypeptide factor that is thought to play a major role in the regulation of proliferation of many cell types and various differentiation processes. Several related isoforms have been structurally characterized, three of which, TGF-beta 1, -beta 2, and -beta 3, ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Lopez AR,Cook J,Deininger PL,Derynck R

    更新日期:1992-04-01 00:00:00

  • POU transcription factors Brn-3a and Brn-3b interact with the estrogen receptor and differentially regulate transcriptional activity via an estrogen response element.

    abstract::The estrogen receptor (ER) modulates transcription by forming complexes with other proteins and then binding to the estrogen response element (ERE). We have identified a novel interaction of this receptor with the POU transcription factors Brn-3a and Brn-3b which was independent of ligand binding. By pull-down assays ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Budhram-Mahadeo V,Parker M,Latchman DS

    更新日期:1998-02-01 00:00:00

  • Adenine transport and binding in cultured mammalian cells deficient in adenine phosphoribosyltransferase.

    abstract::Rapid kinetic techniques were employed to measure the transport of adenine in adenine phosphoribosyltransferase-deficient L929 and Chinese hamster ovary (CHO) cells in zero-trans entry and exit and equilibrium exchange procedures. The kinetic parameters of transport were computed by fitting appropriate integrated rate...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Puziss MB,Wohlhueter RM,Plagemann PG

    更新日期:1983-01-01 00:00:00

  • Induced focal adhesion kinase (FAK) expression in FAK-null cells enhances cell spreading and migration requiring both auto- and activation loop phosphorylation sites and inhibits adhesion-dependent tyrosine phosphorylation of Pyk2.

    abstract::Focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase involved in integrin-mediated control of cell behavior. Following cell adhesion to components of the extracellular matrix, FAK becomes phosphorylated at multiple sites, including tyrosines 397, 576, and 577. Tyr-397 is an autophosphorylation site tha...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Owen JD,Ruest PJ,Fry DW,Hanks SK

    更新日期:1999-07-01 00:00:00

  • MAT1-modulated CAK activity regulates cell cycle G(1) exit.

    abstract::The cyclin-dependent kinase (CDK)-activating kinase (CAK) is involved in cell cycle control, transcription, and DNA repair (E. A. Nigg, Curr. Opin. Cell. Biol. 8:312-317, 1996). However, the mechanisms of how CAK is integrated into these signaling pathways remain unknown. We previously demonstrated that abrogation of ...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Wu L,Chen P,Shum CH,Chen C,Barsky LW,Weinberg KI,Jong A,Triche TJ

    更新日期:2001-01-01 00:00:00

  • Regulation of the nuclear genes encoding the cytoplasmic and mitochondrial leucyl-tRNA synthetases of Neurospora crassa.

    abstract::We show that the nuclear genes for the cytoplasmic and mitochondrial leucyl-tRNA synthetase (LeuRS) of Neurospora crassa are distinct in their encoded proteins, codon usage, mRNA levels, and regulation. The 4.2-kilobase-pair region representing the structural gene for cytoplasmic LeuRS and flanking regions has been se...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Chow CM,Rajbhandary UL

    更新日期:1989-11-01 00:00:00

  • The yeast RSC chromatin-remodeling complex is required for kinetochore function in chromosome segregation.

    abstract::The accurate segregation of chromosomes requires the kinetochore, a complex protein machine that assembles onto centromeric DNA to mediate attachment of replicated sister chromatids to the mitotic spindle apparatus. This study reveals an important role for the yeast RSC ATP-dependent chromatin-remodeling complex at th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Hsu JM,Huang J,Meluh PB,Laurent BC

    更新日期:2003-05-01 00:00:00

  • Interleukin-8 Dedifferentiates Primary Human Luminal Cells to Multipotent Stem Cells.

    abstract::During aging, cellular plasticity and senescence play important roles in tissue regeneration and the pathogenesis of different diseases, including cancer. We have recently shown that senescent breast luminal cells can activate their adjacent stromal fibroblasts. In the present report, we present clear evidence that th...

    journal_title:Molecular and cellular biology

    pub_type: 杂志文章


    authors: Al-Khalaf HH,Ghebeh H,Wakil SM,Al-Mohanna F,Aboussekhra A

    更新日期:2020-04-13 00:00:00