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A CK2-RNF4 interplay coordinates non-canonical SUMOylation and degradation of nuclear receptor FXR

Journal of Molecular Cell Biology 2017年第3期9卷 195-208页

作者： Stephanie Bilodeau Veronique Caron jonathan gagnon Alexandre Kuftedjian Andre Tremblay Research Center CHU Sainte-Justine Montreal Quebec H3T 1C5 Canada Department of Biochemistry and Molecular Medicine Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada Department of Obstetrics & Gynecology Faculty of Medicine University of Montreal Montreal Quebec H3T 1J4 Canada

Farnesoid X receptor （FXR） is a ligand-activated nuclear receptor that plays a central role in regulating genes involved in bile acid homeostasis, and fat and glucose metabolism. Here, we demonstrate a post-translational interplay between FXR phosphoryl- ation, SUMOylation, and ubiquitination that directs the receptor into an activation-degradation pathway in hepatocytes. We iden- tify a non-canonical SUMOylation motif termed pSuM that conjugates SUM02 at Lys-325 of FXR under the direct control of casein kinase 2 （CK2）, which provides the required negative charge for Ubc9 and PIAS1 to perform SUMOylation, by phosphorylating Ser-327. Lys-325 SUMOylation is indispensable to the promotion of efficient ligand activation and transcriptional coactivation of FXR. Constitutive pSuM activation using a phospho-mimic Ser-327 mutant or catalytic CK2 expression strongly induces SUM02 conjugation, which directs FXR ubiquitination and proteasome-dependent degradation. We also determine that such SUMOylation-dependent ubiquitination of FXR is mediated by the E3 ubiquitin ligase RNF4, which is required to achieve maximal induction of FXR and optimal up- or downregulation of responsive genes involved in bile acid homeostasis and liver regeneration. Our findings identify a highly regulated atypical SUMO conjugation motif that serves to coordinate FXR transcriptional compe- tence, thereby expanding the intricate dynamics of the SUMOylation process used by incoming signals to govern metabolic gene regulation.

关键词： farnesoid receptor SUMOylation ubiquitination 26S proteasome bile acid

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On the Improvement of Wind Power Predictions Based on Terrain Characteristics and Measurements of the Annual Energy Production

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Journal of Flow Control, Measurement & Visualization 2017年第1期5卷 1-20页

作者： jonathan Dorval Christian Masson Yves gagnon Department of Mechanical Engineering &EACUTE cole de technologie supê rieure Montreal Canada Department of Sciences Universit&ecirc de Moncton Edmundston Canada

The assessment of the production capacity of wind farms is a crucial step in wind farm design processes, where a poor assessment can cause significant economic losses. Data from Canadian wind farms benefiting from national production incentive programs show that wind farms are typically characterized by an overestimation of the production capacity. In this context, a study has been done to provide insight on the origin of the discrepancies between the energy production estimates and the measured energy generation, and to develop a method to reduce these discrepancies. To this end, the WAsP and MS-Micro models have been studied. Besides the wind speed measurements, topography indices have been developed to identify the influence of the various characteristics of the site on the error in the annual energy production (AEP). In addition, roughness classes have been created, including a reference roughness and a roughness complexity. The indices have also allowed establishing correlations and developing equations to evaluate the error based on the site characteristics and the positions of wind turbines on the measured annual energy production. An average reduction of up to 83% on the AEP errors was obtained when the methodology was applied to five wind farms in Canada.

关键词： Wind Energy Wind Farm Assessment WAsP MS-Micro Roughness Classes Roughness Complexity

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