51 research outputs found

    A human MAP kinase interactome.

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    Mitogen-activated protein kinase (MAPK) pathways form the backbone of signal transduction in the mammalian cell. Here we applied a systematic experimental and computational approach to map 2,269 interactions between human MAPK-related proteins and other cellular machinery and to assemble these data into functional modules. Multiple lines of evidence including conservation with yeast supported a core network of 641 interactions. Using small interfering RNA knockdowns, we observed that approximately one-third of MAPK-interacting proteins modulated MAPK-mediated signaling. We uncovered the Na-H exchanger NHE1 as a potential MAPK scaffold, found links between HSP90 chaperones and MAPK pathways and identified MUC12 as the human analog to the yeast signaling mucin Msb2. This study makes available a large resource of MAPK interactions and clone libraries, and it illustrates a methodology for probing signaling networks based on functional refinement of experimentally derived protein-interaction maps

    Thyrotroph Embryonic Factor Regulates Light-Induced Transcription of Repair Genes in Zebrafish Embryonic Cells

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    Numerous responses are triggered by light in the cell. How the light signal is detected and transduced into a cellular response is still an enigma. Each zebrafish cell has the capacity to directly detect light, making this organism particularly suitable for the study of light dependent transcription. To gain insight into the light signalling mechanism we identified genes that are activated by light exposure at an early embryonic stage, when specialised light sensing organs have not yet formed. We screened over 14,900 genes using micro-array GeneChips, and identified 19 light-induced genes that function primarily in light signalling, stress response, and DNA repair. Here we reveal that PAR Response Elements are present in all promoters of the light-induced genes, and demonstrate a pivotal role for the PAR bZip transcription factor Thyrotroph embryonic factor (Tef) in regulating the majority of light-induced genes. We show that tefβ transcription is directly regulated by light while transcription of tefα is under circadian clock control at later stages of development. These data leads us to propose their involvement in light-induced UV tolerance in the zebrafish embryo

    Emerging roles of ATF2 and the dynamic AP1 network in cancer

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    Cooperation among transcription factors is central for their ability to execute specific transcriptional programmes. The AP1 complex exemplifies a network of transcription factors that function in unison under normal circumstances and during the course of tumour development and progression. This Perspective summarizes our current understanding of the changes in members of the AP1 complex and the role of ATF2 as part of this complex in tumorigenesis.Fil: Lopez Bergami, Pablo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Lau, Eric . Burnham Institute for Medical Research; Estados UnidosFil: Ronai, Zeev . Burnham Institute for Medical Research; Estados Unido

    Unmet needs and current and future approaches for osteoporotic patients at high risk of hip fracture

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    Habitat value of subsea wells and pipelines for fishery target species in Australia

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    Subsea pipelines and wells installed to support the oil and gas industry represent some of the most extensive and numerous anthropogenic structures throughout global marine ecosystems. There remains a paucity of information on the habitat value of these structures for fishery target species and, as a result, little understanding of how decommissioning should be conducted to minimise impacts to populations of these economically and socially important species. We assess the diversity and abundance of species that are targets of recreational and commercial fisheries on 33 subsea wells and 17 pipelines across the tropical northwest and temperate southeast marine regions of Australia. We examine relationships between fish identity and abundance and a range of environmental (e.g., depth, location), infrastructure-specific (e.g., pipeline position, diameter, age, length of pipeline, height of well, position on well), and biological (% cover of epibiota) variables using video filmed by remotely operated vehicles during their routine offshore inspection and maintenance campaigns. A total of 100 fishery target species were observed across subsea well and pipeline infrastructure, 56 species uniquely observed on pipelines and nine unique to wells. The families Lutjanidae (snapper), Serranidae (rock cods, groupers, perch), and Carangidae (trevallies) were most common and abundant on both wells and pipelines. In the northwest, lutjanids were most abundant around the base of wells, in shallow depths, on shorter wells, and where pipelines spanned the seafloor. A greater number of fishery target species and abundance of ocean perch (Helicolenus spp.) were also associated with pipelines that spanned the seafloor in temperate southeast Australia. The combined biomass of three species of snapper on wells in the northwest was 1,270 kg, with production levels for these species on each well estimated to be 105.2 g m2 year-1. The present study serves as an important reference point for informing decommissioning decisions for pipeline and well infrastructure and demonstrates the utility of industry-held data for science. We suggest that key predictor variables identified here be incorporated into comprehensive before-after-control-impact scientific studies for specific fields/assets to enable the prediction of potential impacts of decommissioning scenarios on marine communities present and quantification of such impacts after the decommissioning activity has occurred
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