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https://www.readbyqxmd.com/read/27913212/vcp-cooperates-with-ubxd1-to-degrade-mitochondrial-outer-membrane-protein-mcl1-in-model-of-huntington-s-disease
#1
Xing Guo, Xin Qi
Proteasome-dependent turnover of mitochondrial outer membrane (OMM)-associated proteins is one of the mechanisms for maintaining proper mitochondrial quality and function. However, the underlying pathways and their implications in human disease are poorly understood. Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder caused by expanded CAG repeats in the N terminal of the huntingtin gene (mutant Huntingtin, mtHtt). In this study, we show an extensive degradation of the OMM protein MCL1 (Myeloid cell leukemia sequence 1) in both HD mouse striatal cells and HD patient fibroblasts...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27900343/divergence-and-rewiring-of-regulatory-networks-for-neural-development-between-human-and-other-species
#2
COMMENT
Ping Wang, Dejian Zhao, Shira Rockowitz, Deyou Zheng
Neural and brain development in human and other mammalian species are largely similar, but distinct features exist at the levels of macrostructure and underlying genetic control. Comparative studies of epigenetic regulation and transcription factor (TF) binding in humans, chimpanzees, rodents, and other species have found large differences in gene regulatory networks. A recent analysis of the cistromes of REST/NRSF, a critical transcriptional regulator for the nervous system, demonstrated that REST binding to syntenic genomic regions (i...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27899587/temporal-self-regulation-of-transposition-through-host-independent-transposase-rodlet-formation
#3
Lauren E Woodard, Laura M Downes, Yi-Chien Lee, Aparna Kaja, Eyuel S Terefe, Matthew H Wilson
Transposons are highly abundant in eukaryotic genomes, but their mobilization must be finely tuned to maintain host organism fitness and allow for transposon propagation. Forty percent of the human genome is comprised of transposable element sequences, and the most abundant cut-and-paste transposons are from the hAT superfamily. We found that the hAT transposase TcBuster from Tribolium castaneum formed filamentous structures, or rodlets, in human tissue culture cells, after gene transfer to adult mice, and ex vivo in cell-free conditions, indicating that host co-factors or cellular structures were not required for rodlet formation...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27897008/tracing-co-regulatory-network-dynamics-in-noisy-single-cell-transcriptome-trajectories
#4
Pablo Cordero, Joshua M Stuart
The availability of gene expression data at the single cell level makes it possible to probe the molecular underpinnings of complex biological processes such as differentiation and oncogenesis. Promising new methods have emerged for reconstructing a progression 'trajectory' from static single-cell transcriptome measurements. However, it remains unclear how to adequately model the appreciable level of noise in these data to elucidate gene regulatory network rewiring. Here, we present a framework called Single Cell Inference of MorphIng Trajectories and their Associated Regulation (SCIMITAR) that infers progressions from static single-cell transcriptomes by employing a continuous parametrization of Gaussian mixtures in high-dimensional curves...
2016: Pacific Symposium on Biocomputing
https://www.readbyqxmd.com/read/27889632/synthesis-biological-evaluation-and-in-silico-molecular-modeling-of-pyrrolyl-benzohydrazide-derivatives-as-enoyl-acp-reductase-inhibitors
#5
Shrinivas D Joshi, Sheshagiri R Dixit, Venkatarao H Kulkarni, Christian Lherbet, Mallikarjuna N Nadagouda, Tejraj M Aminabhavi
In efforts to develop lead anti-TB compounds, a novel series of 19 pyrrolyl benzohydrazides were synthesized and screened to target enoyl-ACP reductase enzyme, which is one of the important enzymes involved in type II fatty acid biosynthetic pathway of M. tuberculosis. Pharmacophores were constructed using GALAHAD to generate alignment of data sets and calculated by Pareto ranking. The pharmacophore features were then filtered by Surflex-dock study using enoyl ACP reductase from M. tuberculosis. Compounds 5b and 5d showed H-bonding interactions with Tyr158, Thr196 and co-factor NAD(+) that fitted well within the binding pocket of InhA...
November 17, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27889449/phosphorylated-ctip-functions-as-a-co-factor-of-the-mre11-rad50-nbs1-endonuclease-in-dna-end-resection
#6
Roopesh Anand, Lepakshi Ranjha, Elda Cannavo, Petr Cejka
To repair a DNA double-strand break (DSB) by homologous recombination (HR), the 5'-terminated strand of the DSB must be resected. The human MRE11-RAD50-NBS1 (MRN) and CtIP proteins were implicated in the initiation of DNA end resection, but the underlying mechanism remained undefined. Here, we show that CtIP is a co-factor of the MRE11 endonuclease activity within the MRN complex. This function is absolutely dependent on CtIP phosphorylation that includes the key cyclin-dependent kinase target motif at Thr-847...
December 1, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27885504/plant-dicer-like-proteins-double-stranded-rna-cleaving-enzymes-for-small-rna-biogenesis
#7
Akihito Fukudome, Toshiyuki Fukuhara
Dicer, a double-stranded RNA (dsRNA)-specific endoribonuclease, plays an essential role in triggering both transcriptional and post-transcriptional gene silencing in eukaryotes by cleaving dsRNAs or single-stranded RNAs bearing stem-loop structures such as microRNA precursor transcripts into 21- to 24-nt small RNAs. Unlike animals, plants have evolved to utilize at least four Dicer-like (DCL) proteins. Extensive genetic studies have revealed that each DCL protein participates in a specific gene silencing pathway, with some redundancy...
November 24, 2016: Journal of Plant Research
https://www.readbyqxmd.com/read/27883078/impaired-endothelial-nitric-oxide-synthase-homodimer-formation-triggers-development-of-transplant-vasculopathy-insights-from-a-murine-aortic-transplantation-model
#8
Rupert Oberhuber, Gregor Riede, Benno Cardini, David Bernhard, Barbara Messner, Katrin Watschinger, Christina Steger, Gerald Brandacher, Johann Pratschke, Georg Golderer, Ernst R Werner, Manuel Maglione
Transplant vasculopathy (TV) represents a major obstacle to long-term graft survival and correlates with severity of ischemia reperfusion injury (IRI). Donor administration of the nitric oxide synthases (NOS) co-factor tetrahydrobiopterin has been shown to prevent IRI. Herein, we analysed whether tetrahydrobiopterin is also involved in TV development. Using a fully allogeneic mismatched (BALB/c to C57BL/6) murine aortic transplantation model grafts subjected to long cold ischemia time developed severe TV with intimal hyperplasia (α-smooth muscle actin positive cells in the neointima) and endothelial activation (increased P-selectin expression)...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27876555/one-carbon-metabolism-and-epigenetics
#9
REVIEW
Simonetta Friso, Silvia Udali, Domenica De Santis, Sang-Woon Choi
The function of one-carbon metabolism is that of regulating the provision of methyl groups for biological methylation reactions including that of DNA and histone proteins. Methylation at specific sites into the DNA sequence and at histone tails are among the major epigenetic feature of mammalian genome for the regulation of gene expression. The enzymes within one-carbon metabolism are dependent from a number of vitamins or nutrients that serve either as co-factors or methyl acceptors or donors among which folate, vitamin B12, vitamin B6, betaine, choline and methionine have a major role...
November 19, 2016: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/27871484/identification-of-a-nuclear-exosome-decay-pathway-for-processed-transcripts
#10
Nicola Meola, Michal Domanski, Evdoxia Karadoulama, Yun Chen, Coline Gentil, Dennis Pultz, Kristoffer Vitting-Seerup, Søren Lykke-Andersen, Jens S Andersen, Albin Sandelin, Torben Heick Jensen
The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its co-factor Mtr4p/hMTR4, which links to RNA-binding protein adaptors. One example is the trimeric human nuclear exosome targeting (NEXT) complex, which is composed of hMTR4, the Zn-finger protein ZCCHC8, and the RNA-binding factor RBM7. NEXT primarily targets early and unprocessed transcripts, which demands a rationale for how the nuclear exosome recognizes processed RNAs. Here, we describe the poly(A) tail exosome targeting (PAXT) connection, which comprises the ZFC3H1 Zn-knuckle protein as a central link between hMTR4 and the nuclear poly(A)-binding protein PABPN1...
November 3, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27868087/diabetic-wound-healing-and-activation-of-nrf2-by-herbal-medicine
#11
Donald R Senger, Shugeng Cao
Nrf2 defense is a very important cellular mechanism to control oxidative stress, which is implicated in wound healing. Nrf2 can induce many cytoprotective genes, including HO-1, NQO1 and G6PD. Among many natural products that have been reported as Nrf2 activators, sulforaphane and curcumin have been studied more widely than any others, and both are in clinical trials for non-cancerous disorders. Recently, we reported 4-ethyl catechol and 4-vinyl catechol as Nrf2 co-factors that can induce Nrf2 as potently as sulforaphane and curcumin...
2016: Journal of Nature and Science
https://www.readbyqxmd.com/read/27867533/the-hect-domain-ubiquitin-ligase-huwe1-targets-unassembled-soluble-proteins-for-degradation
#12
Yue Xu, D Eric Anderson, Yihong Ye
In eukaryotes, many proteins function in multi-subunit complexes that require proper assembly. To maintain complex stoichiometry, cells use the endoplasmic reticulum-associated degradation system to degrade unassembled membrane subunits, but how unassembled soluble proteins are eliminated is undefined. Here we show that degradation of unassembled soluble proteins (referred to as unassembled soluble protein degradation, USPD) requires the ubiquitin selective chaperone p97, its co-factor nuclear protein localization protein 4 (Npl4), and the proteasome...
2016: Cell Discovery
https://www.readbyqxmd.com/read/27867007/srf-co-factors-control-the-balance-between-cell-proliferation-and-contractility
#13
Francesco Gualdrini, Cyril Esnault, Stuart Horswell, Aengus Stewart, Nik Matthews, Richard Treisman
The ERK-regulated ternary complex factors (TCFs) act with the transcription factor serum response factor (SRF) to activate mitogen-induced transcription. However, the extent of their involvement in the immediate-early transcriptional response, and their wider functional significance, has remained unclear. We show that, in MEFs, TCF inactivation significantly inhibits over 60% of TPA-inducible gene transcription and impairs cell proliferation. Using integrated SRF ChIP-seq and Hi-C data, we identified over 700 TCF-dependent SRF direct target genes involved in signaling, transcription, and proliferation...
November 5, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27865623/key-role-of-an-adp-ribose-dependent-transcriptional-regulator-of-nad-metabolism-for-fitness-and-virulence-of-pseudomonas-aeruginosa
#14
Elza Okon, Sarah Dethlefsen, Anna Pelnikevich, Andrea van Barneveld, Antje Munder, Burkhard Tümmler
NAD is an essential co-factor of redox reactions and metabolic conversions of NAD-dependent enzymes. NAD biosynthesis in the opportunistic pathogen Pseudomonas aeruginosa has yet not been experimentally explored. The in silico search for orthologs in the P. aeruginosa PAO1 genome identified the operon pncA - pncB1-nadE (PA4918-PA4920) to encode the nicotinamidase, nicotinate phosporibosyltransferase and Nad synthase of salvage pathway I. The functional role of the preceding genes PA4917 and PA4916 was resolved by the characterization of recombinant protein...
November 5, 2016: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/27854316/causes-consequences-and-public-health-implications-of-low-b-vitamin-status-in-ageing
#15
REVIEW
Kirsty Porter, Leane Hoey, Catherine F Hughes, Mary Ward, Helene McNulty
The potential protective roles of folate and the metabolically related B-vitamins (vitamins B12, B6 and riboflavin) in diseases of ageing are of increasing research interest. The most common cause of folate and riboflavin deficiencies in older people is low dietary intake, whereas low B12 status is primarily associated with food-bound malabsorption, while sub-optimal vitamin B6 status is attributed to increased requirements in ageing. Observational evidence links low status of folate and the related B-vitamins (and/or elevated concentrations of homocysteine) with a higher risk of degenerative diseases including cardiovascular disease (CVD), cognitive dysfunction and osteoporosis...
November 16, 2016: Nutrients
https://www.readbyqxmd.com/read/27847355/crystal-structure-of-the-marburg-virus-vp35-oligomerization-domain
#16
Jessica F Bruhn, Robert N Kirchdoerfer, Sarah M Urata, Sheng Li, Ian J Tickle, Gérard Bricogne, Erica Ollmann Saphire
: Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a distinct genus from Ebola virus (EBOV) (genera Marburgvirus and Ebolavirus). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase co-factor, a viral protein chaperone and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain...
November 9, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27845713/novel-approaches-to-investigate-one-carbon-metabolism-and-related-b-vitamins-in-blood-pressure
#17
REVIEW
Amy McMahon, Helene McNulty, Catherine F Hughes, J J Strain, Mary Ward
Hypertension, a major risk factor for heart disease and stroke, is the world's leading cause of preventable, premature death. A common polymorphism (677C→T) in the gene encoding the folate metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) is associated with increased blood pressure, and there is accumulating evidence demonstrating that this phenotype can be modulated, specifically in individuals with the MTHFR 677TT genotype, by the B-vitamin riboflavin, an essential co-factor for MTHFR. The underlying mechanism that links this polymorphism, and the related gene-nutrient interaction, with hypertension is currently unknown...
November 11, 2016: Nutrients
https://www.readbyqxmd.com/read/27837013/partial-reconstitution-of-the-rnai-response-in-human-cells-using-drosophila-gene-products
#18
Edward M Kennedy, Anand V R Kornepati, Hal P Bogerd, Bryan R Cullen
While mammalian somatic cells are incapable of mounting an effective RNA interference (RNAi) response to viral infections, plants and invertebrates are able to generate high levels of viral short interfering RNAs (siRNAs) that can control many infections. In Drosophila, the RNAi response is mediated by the Dicer 2 enzyme (dDcr2) acting in concert with two co-factors called Loqs-PD and R2D2. To examine whether a functional RNAi response could be mounted in human somatic cells, we expressed dDcr2, in the presence or absence of Loqs-PD and/or R2D2, in a previously described human cell line, NoDice/ΔPKR, that lacks functional forms of human Dicer (hDcr) and PKR...
November 11, 2016: RNA
https://www.readbyqxmd.com/read/27830506/vitamin-a-as-pkc-co-factor-and-regulator-of-mitochondrial-energetics
#19
Ulrich Hammerling
For the past century, vitamin A has been considered to serve as a precursor for retinoids that facilitate vision or as a precursor for retinoic acid (RA), a signaling molecule that modulates gene expression. However, vitamin A circulates in plasma at levels that far exceed the amount needed for vision or the synthesis of nanomolar levels of RA, and this suggests that vitamin A alcohol (i.e. retinol) may possess additional biological activity. We have pursued this question for the last 20 years, and in this chapter, we unfold the story of our quest and the data that support a novel and distinct role for vitamin A (alcohol) action...
2016: Sub-cellular Biochemistry
https://www.readbyqxmd.com/read/27829167/atf3-modulates-calcium-signaling-in-osteoclast-differentiation-and-activity-by-associating-with-c-fos-and-nfatc1-proteins
#20
Byung-Chul Jeong, Jung Ha Kim, Kabsun Kim, Inyoung Kim, Semun Seong, Nacksung Kim
Activating transcription factor 3 (ATF3), a member of the ATF/cAMP response element-binding protein family of transcription factors, has been implicated in the regulation of cell proliferation and differentiation. However, whether ATF3 is involved in osteoclast differentiation and activity has not been well-studied. In the present study, we examined the role of ATF3 in osteoclast differentiation and function. ATF3 expression was down-regulated during RANKL-induced osteoclast differentiation. Overexpression of ATF3 in bone marrow-derived monocyte/macrophage lineage cells (BMMs) promoted osteoclast differentiation and activity and strongly induced the expression of osteoclast genes encoding nuclear factor of activated T-cells c1 (NFATc1) and tartrate-resistant acid phosphatase (TRAP) compared to that in the control group...
November 6, 2016: Bone
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