38 research outputs found

    MLN51 Stimulates the RNA-Helicase Activity of eIF4AIII

    Get PDF
    The core of the exon-junction complex consists of Y14, Magoh, MLN51 and eIF4AIII, a DEAD-box RNA helicase. MLN51 stimulates the ATPase activity of eIF4AIII, whilst the Y14-Magoh complex inhibits it. We show that the MLN51-dependent stimulation increases both the affinity of eIF4AIII for ATP and the rate of enzyme turnover; the K (M) is decreased by an order of magnitude and k (cat) increases 30 fold. Y14-Magoh do inhibit the MLN51-stimulated ATPase activity, but not back to background levels. The ATP-bound form of the eIF4AIII-MLN51 complex has a 100-fold higher affinity for RNA than the unbound form and ATP hydrolysis reduces this affinity. MLN51 stimulates the RNA-helicase activity of eIF4AIII, suggesting that this activity may be functionally important

    Mol Biol Cell

    Get PDF
    The exon junction complex (EJC) is loaded onto mRNAs as a consequence of splicing and regulates multiple posttranscriptional events. MLN51, Magoh, Y14, and eIF4A3 form a highly stable EJC core, but where this tetrameric complex is assembled in the cell remains unclear. Here we show that EJC factors are enriched in domains that we term perispeckles and are visible as doughnuts around nuclear speckles. Fluorescence resonance energy transfer analyses and EJC assembly mutants show that perispeckles do not store free subunits, but instead are enriched for assembled cores. At the ultrastructural level, perispeckles are distinct from interchromatin granule clusters that may function as storage sites for splicing factors and intermingle with perichromatin fibrils, where nascent RNAs and active RNA Pol II are present. These results support a model in which perispeckles are major assembly sites for the tetrameric EJC core. This subnuclear territory thus represents an intermediate region important for mRNA maturation, between transcription sites and splicing factor reservoirs and assembly sites

    The Role of Creativity in Entrepreneurship

    Get PDF
    This paper evaluates the contribution of creativity to entrepreneurship theory and practice in terms of building an holistic and transdisciplinary understanding of its impact. Acknowledgement is made of the subjectivist theory of entrepreneurship which embraces randomness, uncertainty and ambiguity but these factors should then be embedded in wider business and social contexts. The analysis is synthesised into a number of themes, from consideration of its definition, its link with personality and cognitive style, creativity as a process and the use of biography in uncovering data on creative entrepreneurial behaviour. Other relevant areas of discussion include creativity’s link with motivation, actualisation and innovation, as well as the interrogation of entrepreneurial artists as owner/managers. These factors are embedded in a critical evaluation of how creativity contributes to successful entrepreneurship practice. Modelling, measuring and testing entrepreneurial creativity are also considered and the paper includes detailed consideration of several models of creativity in entrepreneurship. Recommendations for future theory and practice are also made

    TRAF4 is a novel phosphoinositide-binding protein modulating tight junctions and favoring cell migration

    Get PDF
    Tumor necrosis factor (TNF) receptor-associated factor 4 (TRAF4) is frequently overexpressed in carcinomas, suggesting a specific role in cancer. Although TRAF4 protein is predominantly found at tight junctions (TJs) in normal mammary epithelial cells (MECs), it accumulates in the cytoplasm of malignant MECs. How TRAF4 is recruited and functions at TJs is unclear. Here we show that TRAF4 possesses a novel phosphoinositide (PIP)-binding domain crucial for its recruitment to TJs. Of interest, this property is shared by the other members of the TRAF protein family. Indeed, the TRAF domain of all TRAF proteins (TRAF1 to TRAF6) is a bona fide PIP-binding domain. Molecular and structural analyses revealed that the TRAF domain of TRAF4 exists as a trimer that binds up to three lipids using basic residues exposed at its surface. Cellular studies indicated that TRAF4 acts as a negative regulator of TJ and increases cell migration. These functions are dependent from its ability to interact with PIPs. Our results suggest that TRAF4 overexpression might contribute to breast cancer progression by destabilizing TJs and favoring cell migration

    CASC3 (cancer susceptibility candidate 3)

    Get PDF
    Review on CASC3 (cancer susceptibility candidate 3), with data on DNA, on the protein encoded, and where the gene is implicated

    GRB10 (growth factor receptor-bound protein 10)

    Get PDF
    Review on GRB10 (growth factor receptor-bound protein 10), with data on DNA, on the protein encoded, and where the gene is implicated

    From Fact Check to Counterattack

    No full text

    The Soviet Picture Postcard as a Transmedial Object of Mass Culture and Ideological Practice

    No full text
    Matteo Bertelé focuses on Soviet picture postcards as an object of mass culture and ideological practice using a selection of postcards from the Alberto Sandretti Collection. He explores the different functions of postcards within Soviet visual culture between two poles: their original purpose to create a unitary, organic and canonical Soviet imagery and their diverse private applications and adaptations to everyday life.Sowjetische Bildpostkarten vereinten in ihrer Entstehung zahlreiche Techniken von der Malerei über die Fotografie bis hin zur Grafik. Die Postkarten erfüllten in der sowjetischen visuellen Kultur eine Reihe von Funktionen. Diese bewegten sich im Spannungsfeld zwischen der offiziellen Agenda, eine einheitliche, organische und verbindliche sowjetische Bildwelt, einen Kanon, zu schaffen einerseits, und den vielfältigen Formen und Praktiken des Gebrauchs der Karten im Alltag andererseits
    corecore