Ubiquitin-specific protease 12 interacting partners Uaf-1 and WDR20 are potential therapeutic targets in prostate cancer

The androgen receptor (AR) is a key transcription factor in the initiation and progression of prostate cancer (PC) and is a major therapeutic target for the treatment of advanced disease. Unfortunately, current therapies are not curative for castration resistant PC and a better understanding of AR regulation could identify novel therapeutic targets and biomarkers to aid treatment of this disease. The AR is known to be regulated by a number of post-translational modifications and we have recently identified the deubiquitinating enzyme Usp12 as a positive regulator of AR. We determined that Usp12 deubiquitinates the AR resulting in elevated receptor stability and activity. Furthermore, Usp12 silencing was shown to reduce proliferation of PC cells. Usp12 is known to require the co-factors Uaf-1 and WDR20 for catalytic activity. In this report we focus further on the role of Uaf-1 and WDR20 in Usp12 regulation and investigate if these co-factors are also required for controlling AR activity. Firstly, we confirm the presence of the Usp12/Uaf-1/WDR20 complex in PC cells and demonstrate the importance of Uaf-1 and WDR20 for Usp12 stabilisation. Consequently, we show that individual silencing of either Uaf-1 or WDR20 is sufficient to abrogate the activity of the Usp12 complex and down-regulate AR-mediated transcription via receptor destabilisation resulting in increased apoptosis and decreased colony forming ability of PC cells. Moreover, expression of both Uaf-1 and WDR20 is higher in PC tissue compared to benign controls. Overall these results highlight the potential importance of the Usp12/Uaf-1/WDR20 complex in AR regulation and PC progression. Androgen receptor is a key transcriptional regulator in prostate cancer. Usp12/Uaf-1/WDR20 complex plays a crucial role in androgen receptor stability and activity. Destabilising an individual Usp12/Uaf-1/WDR20 complex member reduces the protein levels of the whole complex and diminishes androgen receptor activity. Protein levels of all members of the Usp12/Uaf-1/WDR20 complex are significantly increased in PC

Factors influencing the internationalisation of new ventures in the Irish aquaculture industry: An exploratory study

International new ventures, Industry structure, Low-technology sector, Ireland,

Patterns and Trends in Urban Biodiversity and Landscape Design

Urbanization destroys or modifi es native habitats and creates new ones with its infrastructure. Because of these changes, urban landscapes favor non-native and native species that are generalists. Nevertheless, cities reveal a great variety of habitats and species, and, especially in temperate cities, the diversity of vascular plants and birds can be higher than in the surrounding landscapes. The actual occurrence of a species, however, depends on habitat availability and quality, the spatial arrangements of habitats, species pools, a species’ adaptability and natural history, and site history. In addition, cities are particularly human-made ecological systems. Top- down and bottom-up activities of planners, land managers, and citizens create the urban biodiversity in general and in detail. Plants and animals in cities are the everyday life contact with nature of the most humans on our earth. The intrinsic interplay of social and ecological systems with a city often forms unique biotic assemblages inherent to that city. To support native biodiversity, landscape architects, conservation biologists, and other groups are linking landscape design with ecosystem structure and function to create and restore habitats and reintroduce native species in cities