Journal of Biological Chemistry (J Biol Chem)

Publisher: American Society for Biochemistry and Molecular Biology, American Society for Biochemistry and Molecular Biology

Journal description

Complete content of the Journal of Biological Chemistry as of April 1995.

Current impact factor: 4.57

Impact Factor Rankings

2016 Impact Factor Available summer 2017
2014 / 2015 Impact Factor 4.573
2013 Impact Factor 4.6
2012 Impact Factor 4.651
2011 Impact Factor 4.773
2010 Impact Factor 5.328
2009 Impact Factor 5.328
2008 Impact Factor 5.52
2007 Impact Factor 5.581
2006 Impact Factor 5.808
2005 Impact Factor 5.854
2004 Impact Factor 6.355
2003 Impact Factor 6.482
2002 Impact Factor 6.696
2001 Impact Factor 7.258
2000 Impact Factor 7.368
1999 Impact Factor 7.666
1998 Impact Factor 7.199
1997 Impact Factor 6.963
1996 Impact Factor 7.452
1995 Impact Factor 7.385
1994 Impact Factor 7.716
1993 Impact Factor 6.793
1992 Impact Factor 6.733

Impact factor over time

Impact factor
Year

Additional details

5-year impact 4.69
Cited half-life >10.0
Immediacy index 0.89
Eigenfactor 0.54
Article influence 1.74
Website Journal of Biological Chemistry website
Other titles Journal of biological chemistry (Online), Journal of biological chemistry, JBC online, JBC
ISSN 1083-351X
OCLC 32808313
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

American Society for Biochemistry and Molecular Biology

  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • Authors accepted peer-reviewed manuscript may be posted on an institutional repository
    • Publisher copyright and source must be acknowledged with set phrase: "This research was originally published in Journal Name. Author(s). Title. Journal Name. Year. Vol:pp-pp. © the American Society for Biochemistry and Molecular Biology"
    • On a non-profit server
    • Publisher's version/PDF cannot be used
  • Classification
    white

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Lysine methylation of non-histone proteins has emerged as a key regulator of many cellular functions. Although less studied than other post-translational modifications such as phosphorylation and acetylation, the number of known methylated non-histone proteins is rapidly expanding. We have identified the p21-activated kinase 4 (PAK4) as a new substrate for methylation by the protein lysine methyltransferase SETD6. Our data demonstrate that SETD6 methylates PAK4 both in vitro and at chromatin in cells. Interestingly, depletion of SETD6 in various cellular systems significantly hinders the activation of the Wnt/β-catenin target genes. PAK4 was recently shown to regulate β-catenin signaling, and we show that SETD6 is a key mediator of this pathway. In the presence of SETD6, the physical interaction between PAK4 and β-catenin is dramatically increased, leading to a significant increase in the transcription of β-catenin target genes. Taken together, our results uncover a new regulatory layer of the Wnt/β-catenin signaling cascade and provide new insight into SETD6 biology.
    No preview · Article · Feb 2016 · Journal of Biological Chemistry
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    ABSTRACT: The G-protein-coupled chemokine receptor, CXCR4, generates signals that lead to cell migration, cell proliferation, and other survival mechanisms which result in the metastatic spread of primary tumor cells to distal organs. Numerous studies have demonstrated that CXCR4 can form homodimers, or can heterodimerize with other GPCRs to form receptor complexes that can amplify or decrease the signaling capacity of each individual receptor. Using biophysical and biochemical approaches, we found that CXCR4 can form an induced heterodimer with cannabinoid receptor 2 (CB2) in human breast and prostate cancer cells. Simultaneous, agonist-dependent activation of CXCR4 and CB2 resulted in reduced CXCR4-mediated expression of phosphorylated ERK1/2, and ultimately, reduced cancer cell functions such as calcium mobilization and cellular chemotaxis. Given that treatment with cannabinoids has been shown to reduce invasiveness of cancer cells, as well as CXCR4-mediated migration of immune cells, it is therefore plausible that CXCR4 signaling can be silenced through a physical heterodimeric association with CB2, thereby inhibiting subsequent functions of CXCR4. Taken together, the data illustrates a mechanism by which the cannabinoid system can negatively modulate CXCR4 receptor function, and perhaps, tumor progression.
    No preview · Article · Feb 2016 · Journal of Biological Chemistry
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    ABSTRACT: Recent work from others and us revealed interactions between the Sin3/HDAC complex, the H3K4me3 demethylase KDM5A, GATAD1 and EMSY. Here, we characterize the EMSY/KDM5A/SIN3B complex in detail by quantitative interaction proteomics and ChIP-sequencing. We identify a novel substoichiometric interactor of the complex, transcription factor ZNF131, which recruits EMSY to a large number of active, H3K4me3 marked promoters. Interestingly, using an EMSY knock-out line and subsequent rescue experiments, we show that EMSY is in most cases positively correlated with transcriptional activity of its target genes and stimulates cell proliferation. Finally, by immunohistochemical staining of primary breast tissue microarrays we find that EMSY/KDM5A/SIN3B complex subunits are frequently overexpressed in primary breast cancer cases in a correlative manner. Taken together, these data open venues for exploring the possibility that sporadic breast cancer patients with EMSY amplification might benefit from epigenetic combination therapy targeting both the KDM5A demethylase and histone deacetylases.
    No preview · Article · Feb 2016 · Journal of Biological Chemistry
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    ABSTRACT: The Nrf2 (also known as NFE2L2) transcription factor is a critical regulator of genes involved in defense against oxidative stress. Previous studies suggest that Nrf2 plays a role in adipogenesis in vitro, and deletion of the Nrf2 gene protects against diet-induced obesity in mice. Here, we demonstrate that resistance to diet-induced obesity in Nrf2-/- mice is associated with a 20-30% increase in energy expenditure. Analysis of bioenergetics revealed that Nrf2-/- white adipose tissues (WAT) exhibit greater oxygen consumption. WAT showed a greater than two-fold increase in Ucp1 gene expression. Oxygen consumption is also increased nearly 2.5 fold in Nrf2 deficient fibroblasts. Oxidative stress induced by glucose oxidase resulted in increased Ucp1 expression. Conversely, antioxidant chemicals, such as N-acetylcysteine and MnTBAP, and SB203580, a known suppressor of Ucp1 expression, decreased Ucp1 and oxygen consumption in Nrf2 deficient fibroblasts. These findings suggest that increasing oxidative stress by limiting Nrf2 function in white adipocytes may be a novel means to modulate energy balance as a treatment of obesity and related clinical disorders.
    No preview · Article · Feb 2016 · Journal of Biological Chemistry
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    ABSTRACT: B1 B cells secrete most of the circulating natural antibodies and are considered key effector cells of the innate immune response. However, B1 cell-associated antibodies often cross-react with self-antigens, which leads to autoimmunity, and B1 cells have been implicated in cancer. How B1 cell activity is regulated remains unclear. We show that the Ikaros transcription factor is a major negative regulator of B1 cell development and function. Using conditional knockout mouse models to delete Ikaros at different locations, we show that Ikaros deficient mice exhibit specific and significant increases in splenic and bone marrow B1 cell numbers, and that the B1 progenitor cell pool is increased ∼10-fold in the bone marrow. Ikaros null B1 cells resemble WT B1 cells at the molecular and cellular levels, but show a downregulation of signaling components important for inhibiting proliferation and immunoglobulin production. Ikaros null B1 cells hyper-react to TLR4 stimulation and secrete high amounts of IgM autoantibodies. These results indicate that Ikaros is required to limit B1 cell homeostasis in the adult.
    No preview · Article · Feb 2016 · Journal of Biological Chemistry
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    ABSTRACT: The E3 transcription unit of human species C adenoviruses (Ads) encodes immunomodulatory proteins that mediate direct protection of infected cells. Recently, we described a novel immunomodulatory function for E3/49K, an E3 protein uniquely expressed by species D Ads. E3/49K of Ad19a/Ad64, a serotype that causes epidemic keratokonjunctivitis, is synthesized as a highly glycosylated type I transmembrane protein that is subsequently cleaved resulting in secretion of its large ectodomain (sec49K). Sec49K binds to CD45 on leukocytes, impairing activation and functions of NK cells and T cells. E3/49K is localized in the Golgi/trans-Golgi-network (TGN), early endosomes and on the plasma membrane, yet the cellular compartment where E3/49K is cleaved and the protease involved remained elusive. Here we show that TGN-localized E3/49K comprises both newly-synthesized and recycled molecules. Full-length E3/49K was not detected in late endosomes/lysosomes but the C-terminal fragment accumulated in this compartment at late times of infection. Inhibitor studies showed that cleavage occurs in a post-TGN compartment and that lysosomotropic agents enhance secretion. Interestingly, the cytoplasmic tail of E3/49K contains two potential sorting motifs, YxxΦ and LL that are important for binding the clathrin adaptor proteins AP-1 and AP-2 in vitro. Surprisingly, mutating the LL motif, either alone or together with YxxΦ, did not prevent proteolytic processing, but increased cell surface expression and secretion. Upon Brefeldin-A treatment cell surface expression was rapidly lost, even for mutants lacking all known endocytosis motifs. Together with immunofluorescence data, we propose a model for intracellular E3/49K transport whereby cleavage takes place on the cell surface by matrix-metalloproteases.
    No preview · Article · Feb 2016 · Journal of Biological Chemistry
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    ABSTRACT: Xanthophyllomyces dendrorhous β-fructofuranosidase (XdINV) is a highly glycosylated dimeric enzyme that hydrolyzes sucrose and releases fructose from various fructooligosaccharides (FOS) and fructans. It also catalyzes the synthesis of FOS, prebiotics that stimulate the growth of beneficial bacteria in human gut. In contrast to most fructosylating enzymes, XdINV produces neo-FOS, which makes it an interesting biotechnology target. We present here its three-dimensional structure, which shows the expected bimodular arrangement but, also, a long extension of its C-terminus that together with a N-linked glycan mediate the formation of an unusual dimer. This dimer shapes two active sites communicated by a long channel, which might indicate its potential ability to house branched fructans. This arrangement could be representative of a group of GH32 yeast enzymes having the traits observed in XdINV. Inactivated D80A mutant was used to obtain complexes with relevant substrates and products, their crystals structures showing at least four binding subsites at each active site. Moreover, two different positions are observed from subsite +2 depending of the substrate and, thus, a flexible loop (Glu334-His343) is essential in binding sucrose and β(2-1) linked oligosaccharides. Conversely, β(2-6) and neo-type substrates are accommodated mainly by stacking to Trp105, explaining the production of neokestose and the efficient fructosylating activity of XdINV on α-glucosides. The role of relevant residues has been investigated by mutagenesis and kinetics measurements and a model for the transfructosylating reaction has been proposed. The plasticity of its active site makes XdINV a valuable and flexible biocatalyst to produce novel bioconjugates.
    Preview · Article · Jan 2016 · Journal of Biological Chemistry
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    ABSTRACT: The discovery that the MPC1 and MPC2 genes encode the protein components of the mitochondrial pyruvate carrier (MPC) has invigorated studies of mitochondrial pyruvate transport and its regulation in normal and disease states. Indeed, recent reports have demonstrated MPC involvement in the control of cell fate in cancer and gluconeogenesis in models of type 2 diabetes. Biochemical measurements of MPC activity are foundational for understanding the role of pyruvate transport in health and disease. We developed a 96-well scaled method of 14C-pyruvate uptake that markedly decreases sample requirements and increases throughput relative to previous techniques. This method was applied to determine the mouse liver MPC KM (28.0 ± 3.9 μM) and VMAX (1.08 ± 0.05 nmol/min/mg), which have not previously been reported. KM and VMAX of the rat liver MPC were found to be 71.2 ± 17 μM and 1.42 ± 0.14 nmol/min/mg, respectively. Additionally, we performed parallel pyruvate uptake and oxidation experiments with the same biological samples and show differential results in response to fasting, demonstrating the continued importance of a direct MPC activity assay. We expect this method will be of value for understanding the contribution of the MPC activity to health and disease states where pyruvate metabolism is expected to play a prominent role.
    Preview · Article · Jan 2016 · Journal of Biological Chemistry
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    ABSTRACT: Light Harvesting Complex Stress Related 3 (LHCSR3) is the protein essential for photoprotective excess energy dissipation (non-photochemical quenching, NPQ) in the model green alga Chlamydomonas reinhardtii. Activation of NPQ requires low pH in the thylakoid lumen, which is induced in excess light conditions and sensed by lumen-exposed acidic residues. In this work we have used site-specific mutagenesis in vivo and in vitro for identification of the residues in LHCSR3 that are responsible for sensing lumen pH. Lumen-exposed protonatable residues, aspartate and glutamate, were mutated to asparagine and glutamine, respectively. By expression in a mutant lacking all LHCSR isoforms, residues D117, E221 and E224 were shown to be essential for LHCSR3-dependent NPQ induction in C. reinhardtii. Analysis of recombinant proteins carrying the same mutations refolded in vitro with pigments showed that the capacity of responding to low pH by decreasing the fluorescence lifetime, present in the wild-type protein, was lost. Consistent with a role in pH sensing, the mutations led to a substantial reduction in binding the NPQ inhibitor dicychlohexylcarbodiimide (DCCD).
    Preview · Article · Jan 2016 · Journal of Biological Chemistry
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    ABSTRACT: SiRNA silencing approach has long been used as a method to regulate the expression of specific target gene in vitro and in vivo. However, the effectiveness of delivery and the nonspecific immune stimulatory function of siRNA are the limiting factors for therapeutic application of siRNAs. To overcome these limitations, we developed self-assembled micelle inhibitory RNA (SAMiRNA) nanoparticles made of individually bi-conjugated siRNAs with hydrophilic polymer and lipid on their ends and characterized their stability, immune stimulatory function and in vivo silencing efficacy. SAMiRNAs form very stable nanoparticles with no significant degradation in the size distribution and polydispersity index over 1 year. Overnight incubation of SAMiRNAs (3μM) on murine PBMCs did not cause any significant elaboration of innate immune cytokines such as TNF-α, IL-12 or IL-6, while unmodified siRNAs or liposome or liposome complex significantly stimulated the expression of these cytokines. Lastly, in vivo silencing efficacy of SAMiRNAs was evaluated by targeting amphiregulin (AR) and connective tissue growth factor (CTGF) in bleomycin or TGF-β transgenic (Tg) animal models of pulmonary fibrosis. Only two or three times of intratracheal (i.t.) or intravenous (i.v.) delivery of AR or CTGF SAMiRNAs significantly reduced the bleomycin- or TGF-β -stimulated collagen accumulation in the lung and substantially restored the lung function of TGF-β Tg mice. These studies demonstrated that SAMiRNA nanoparticles as a less-toxic, stable siRNA silencing platform for efficient in vivo targeting of genes implicated in the pathogenesis of pulmonary fibrosis.
    Preview · Article · Jan 2016 · Journal of Biological Chemistry
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    ABSTRACT: West Nile virus (WNV) particles assemble at and bud into the endoplasmic reticulum (ER) and are secreted from infected cells through the secretory pathway. However, the host factor related to these steps is not fully understood. Rab proteins, belonging to the Ras superfamily, play essential roles in regulating many aspects of vesicular trafficking. In this study, we sought to determine which Rab proteins are involved in intracellular trafficking of nascent WNV particles. RNAi analysis revealed that Rab8b plays a role in WNV particle release. We found that Rab8 and WNV antigen were colocalized in WNV-infected human neuroblastoma cells, and that WNV infection enhanced Rab8 expression in the cells. In addition, the amount of WNV particles in the supernatant of Rab8b-deficient cells was significantly decreased compared with that of wild-type cells. We also demonstrated that WNV particles accumulated in the recycling endosomes in WNV-infected cells. In summary, these results suggest that Rab8b is involved in trafficking of WNV particles from recycling endosomes to the plasma membrane.
    Preview · Article · Jan 2016 · Journal of Biological Chemistry
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    ABSTRACT: The structural similarity between the defensins and scorpion neurotoxins suggests that they might have evolved from a common ancestor. However, there is no direct experimental evidence demonstrating functional linkage between scorpion neurotoxin and defensin. The scorpion defensin BmKDfsin4 from Mesobuthus martensii Karsch contains 37 amino acid residues and a conserved CSα/β structural fold. The recombinant BmKDfsin4, a classical defensin, was found to have inhibitory activity against gram-positive bacteria, such as Staphylococcus aureus, Bacillus subtilis and Micrococcus luteus, as well as methicillin-resistant Staphylococcus aureus (MRSA). Interestingly, electrophysiological experiments showed that BmKDfsin4, like scorpion potassium channel neurotoxins, could effectively inhibit Kv1.1, Kv1.2 and Kv1.3 channel currents, and its IC50 value for the Kv1.3 channel was 510.2 nM. Similar to the structure-function relationships of classical scorpion potassium channel-blocking toxins, basic residues (Lys13 and Arg19) of BmKDfsin4 play critical roles in the peptide-Kv1.3 channel interactions. Furthermore, mutagenesis and electrophysiological experiments demonstrated that the channel extracellular pore region is the binding site of BmKDfsin4, indicating that BmKDfsin4 adopts the same mechanism for blocking potassium channel currents as that of classical scorpion toxins. Taken together, our work identifies scorpion BmKDfsin4 as the first invertebrate defensin to block potassium channels. These findings not only demonstrate that defensins from invertebrate animals are a novel type of potassium channel blockers but also provide evidence of functional linkage between the defensins and the neurotoxins.
    Preview · Article · Jan 2016 · Journal of Biological Chemistry
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    ABSTRACT: Cone snail toxins are well-known blockers of voltage-gated sodium channels, a property that is of broad interest in biology and therapeutically in treating neuropathic pain and neurological disorders. While most conotoxin channel blockers function by direct binding to a channel and disrupting its normal ion movement, conotoxin μO§-GVIIJ channel blocking is unique, using both favorable binding interactions with the channel and a direct tether via an intermolecular disulfide bond. Disulfide exchange is possible since conotoxin μO§-GVIIJ contains an S-cysteinylated Cys-24 residue that is capable of exchanging with a free cysteine thiol on the channel surface. Here, we present the solution structure of an analog of μO§-GVIIJ (GVIIJ[C24S]) and the results of structure-activity (SAR) studies with synthetic μO§-GVIIJ variants. GVIIJ[C24S] adopts an inhibitor cystine knot structure, with two antiparallel β-strands stabilized by three disulfide bridges. The loop region linking the β-strands (loop 2) presents residue 24 in a configuration where it could bind to the proposed free cysteine of the channel (Cys-910, rat Nav1.2 numbering; at site 8). The SAR study shows that three residues (Lys-12, Arg-14 and Tyr-16) located in loop 4, and spatially close to residue 24, were also important for functional activity. We propose that the interaction of μO§-GVIIJ with the channel depends on not only disulfide tethering via Cys-24 to a free cysteine at site 8 on the channel, but also the participation of key residues of μO§-GVIIJ on a distinct surface of the peptide.
    Preview · Article · Jan 2016 · Journal of Biological Chemistry
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    ABSTRACT: Adenosine deaminases acting on double-stranded RNA (ADARs) catalyze the deamination of adenosine (A) to produce inosine (I) in double-stranded (ds) RNA structures, a process known as A-to-I RNA editing. DsRNA is an important trigger of innate immune responses, including interferon (IFN) production and action. We examined the role of A-to-I RNA editing by two ADARs, ADAR1 and ADAR2, in the sensing of self RNA in the absence of pathogen infection, leading to activation of IFN-induced, RNA-mediated responses in mouse embryo fibroblasts. IFN treatment of Adar1-/- cells lacking both the p110 constitutive and p150 IFN inducible ADAR1 proteins induced formation of stress granules, whereas neither wild-type (WT) nor Adar2-/- cells displayed a comparable stress granule response following IFN treatment. Phosphorylation of protein synthesis initiation factor eIF2α at serine 51 was increased in IFN-treated Adar1-/- cells but not in either WT or Adar2-/- cells following IFN treatment. Analysis by deep sequencing of mouse exonic loci containing A-to-I editing sites revealed that the majority of editing in MEFs was carried out by ADAR1. IFN treatment increased editing in both WT and Adar2-/- cells, but not in either Adar1-/- or Adar1-/-p150 cells or Stat1-/- or Stat2-/- cells. Hyper-edited sites found in predicted duplex structures showed strand bias of editing for some RNAs. These results implicate ADAR1 p150 as the major A-to-I editor in MEFs, acting as a feedback suppressor of innate immune responses otherwise triggered by self RNAs possessing regions of double-stranded character.
    Preview · Article · Jan 2016 · Journal of Biological Chemistry
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    ABSTRACT: Upon exposure to environmental stress, phosphorylation of the α subunit of eIF2 (eIF2α-P) represses global protein synthesis, coincident with preferential translation of gene transcripts that mitigate stress damage, or alternatively trigger apoptosis. Because there are multiple mammalian eIF2 kinases, each responding to different stress arrangements, this translational control scheme is referred to as the integrated stress response (ISR). Included among the preferentially translated mRNAs induced by eIF2α-P is that encoding the transcription factor CHOP (DDIT3/GADD153). Enhanced levels of CHOP promote cell death when ISR signaling is insufficient to restore cell homeostasis. Preferential translation of CHOP mRNA occurs by a mechanism involving ribosome bypass of an inhibitory upstream ORF (uORF) situated in the 5'-leader of the CHOP mRNA. In this study, we used biochemical and genetic approaches to define the inhibitory features of the CHOP uORF and the biological consequences of loss of the CHOP uORF on CHOP expression during stress. We discovered that specific sequences within the CHOP uORF serve to stall elongating ribosomes and prevent ribosome reinitiation at the downstream CHOP coding sequence. As a consequence, deletion of the CHOP uORF substantially increases the levels and modifies the pattern of induction of CHOP expression in the ISR. Enhanced CHOP expression leads to increased expression of key CHOP-target genes, culminating in increased cell death in response to stress.
    Preview · Article · Jan 2016 · Journal of Biological Chemistry