60 research outputs found

    A Regulatory Mechanism Involving TBP-1/Tat-Binding Protein 1 and Akt/PKB in the Control of Cell Proliferation

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    TBP-1 /Tat-Binding Protein 1 (also named Rpt-5, S6a or PSMC3) is a multifunctional protein, originally identified as a regulator of HIV-1-Tat mediated transcription. It is an AAA-ATPase component of the 19S regulative subunit of the proteasome and, as other members of this protein family, fulfils different cellular functions including proteolysis and transcriptional regulation. We and others reported that over expression of TBP-1 diminishes cell proliferation in different cellular contexts with mechanisms yet to be defined. Accordingly, we demonstrated that TBP-1 binds to and stabilizes the p14ARF oncosuppressor increasing its anti-oncogenic functions. However, TBP-1 restrains cell proliferation also in the absence of ARF, raising the question of what are the molecular pathways involved. Herein we demonstrate that stable knock-down of TBP-1 in human immortalized fibroblasts increases cell proliferation, migration and resistance to apoptosis induced by serum deprivation. We observe that TBP-1 silencing causes activation of the Akt/PKB kinase and that in turn TBP-1, itself, is a downstream target of Akt/PKB. Moreover, MDM2, a known Akt target, plays a major role in this regulation. Altogether, our data suggest the existence of a negative feedback loop involving Akt/PKB that might act as a sensor to modulate TBP-1 levels in proliferating cells

    Using Qualitative Disease Risk Analysis for Herpetofauna Conservation Translocations Transgressing Ecological and Geographical Barriers

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    Through the exploration of disease risk analysis methods employed for four different UK herpetofauna translocations, we illustrate how disease hazards can be identified, and how the risk of disease can be analysed. Where ecological or geographical barriers between source and destination sites exist, parasite populations are likely to differ in identity or strain between the two sites, elevating the risk from disease and increasing the number and category of hazards requiring analysis. Simplification of the translocation pathway through the avoidance of these barriers reduces the risk from disease. The disease risk analysis tool is intended to aid conservation practitioners in decision making relating to disease hazards prior to implementation of a translocation

    Body shape diversification along the benthic-pelagic axis in marine fishes.

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    Colonization of novel habitats can result in marked phenotypic responses to the new environment that include changes in body shape and opportunities for further morphological diversification. Fishes have repeatedly transitioned along the benthic-pelagic axis, with varying degrees of association with the substrate. Previous work focusing on individual lineages shows that these transitions are accompanied by highly predictable changes in body form. Here, we generalize expectations drawn from this literature to study the effects of habitat on body shape diversification across 3344 marine teleost fishes. We compare rates and patterns of evolution in eight linear measurements of body shape among fishes that live in pelagic, demersal and benthic habitats. While average body shape differs between habitats, these differences are subtle compared with the high diversity of shapes found within each habitat. Benthic living increases the rate of body shape evolution and has led to numerous lineages evolving extreme body shapes, including both exceptionally wide bodies and highly elongate, eel-like forms. By contrast, we find that benthic living is associated with the slowest diversification of structures associated with feeding. Though we find that habitat can serve as an impetus for predictable trait changes, we also highlight the diversity of responses in marine teleosts to opportunities presented by major habitats
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