13 research outputs found

    The APC/C and CBP/p300 co-operate to regulate, transcription, transformation and progression through mitosis

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    The anaphase-promoting complex/cyclosome (APC/C) is a multicomponent E3 ubiquitin ligase that, by targeting protein substrates for 26S proteasome-mediated degradation through ubiquitination, coordinates the temporal progression of eukaryotic cells through mitosis and the subsequent G1 phase of the cell cycle. Other functions of the APC/C are, however, less well defined. Here we show that two APC/C components, APC5 and APC7, interact directly with the coactivators CBP and p300 through protein-protein interaction domains that are evolutionarily conserved in adenovirus E1A. This interaction stimulates intrinsic CBP/p300 acetyltransferase activity and potentiates CBP/p300-dependent transcription. We also show that APC5 and APC7 suppress E1A-mediated transformation in a CBP/p300-dependent manner, indicating that these components of the APC/C may be targeted during cellular transformation. Furthermore, we establish that CBP is required in APC/C function; specifically, gene ablation of CBP by RNA-mediated interference markedly reduces the E3 ubiquitin ligase activity of the APC/C and the progression of cells through mitosis. Taken together, our results define discrete roles for the APC/C-CBP/p300 complexes in growth regulation

    The precambrian mafic magmatic record, including large igneous provinces of the kalahari craton and its constituents : A paleogeographic review

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    The study of Precambrian dyke swarms, sill provinces and large igneous provinces on the Kalahari craton in southern Africa has expanded greatly since the pioneering work initiated almost four decades ago. The main contributors to this progress have been a large number of precise U–Pb crystallization ages of mafic rocks, published in a number of recent papers. This information is compiled here into a series of maps that provide a nearly 3 billion year intraplate magmatic record of the Kalahari craton and its earlier constituents, the proto-Kalahari, Kaapvaal and Zimbabwe cratons. We also review their possible paleogeographic relations to other cratons or supercontinents. This review provides a more accessible overview of individual magmatic events, and mostly includes precise U–Pb ages of mafic dykes and sills, some of which can be linked to stratigraphically well-constrained volcanic rocks. The extrusion ages of these volcanic units are also starting to be refined by, among others, in situ dating of baddeleyite. Some mafic dyke swarms, previously characterized entirely on similarity in dyke trends within a swarm, are found to be temporally composite and sometimes consist of up to three different generations. Other mafic dyke swarms, with different trends, can now be linked to protracted volcanic events like the stratigraphically well preserved Mesoarchean Nsuze Group (Pongola Supergroup) and Neoarchean Ventersdorp Supergroup. Following upon these Archean events, shorter-lived Proterozoic large igneous provinces also intrude the Transvaal Supergroup, Olifantshoek Supergroup and Umkondo Group, and include the world’s largest layered intrusion, the Bushveld Complex. Longer-lived late Paleoproterozoic magmatic events are also preserved as mafic intrusions and lava units within the Waterberg and Soutpansberg groups as well as the granitic basement. Many gaps in our knowledge of the Precambrian mafic record of the Kalahari craton remain, but further multi-disciplinary studies combining the latest advances in U–Pb geochronology and both paleomagnetism and geochemistry will help solve the Precambrian paleogeographic puzzle

    Transformation and Tumorigenesis Mediated by the Adenovirus E1A and E1B Oncogenes

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