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The CRL5–SPSB3 ubiquitin ligase targets nuclear cGAS for degradation

Cyclic GMP-AMP synthase (cGAS) senses aberrant DNA during infection, cancer and inflammatory disease, and initiates potent innate immune responses through the synthesis of 2′3′-cyclic GMP-AMP (cGAMP)1–7. The indiscriminate activity of cGAS towards DNA demands tight regulatory mechanisms that are necessary to maintain cell and tissue homeostasis under normal conditions. Inside the cell nucleus, anchoring to nucleosomes and competition with chromatin architectural proteins jointly prohibit cGAS activation by genomic DNA8–15. However, the fate of nuclear cGAS and its role in cell physiology remains unclear. Here we show that the ubiquitin proteasomal system (UPS) degrades nuclear cGAS in cycling cells. We identify SPSB3 as the cGAS-targeting substrate receptor that associates with the cullin–RING ubiquitin ligase 5 (CRL5) complex to ligate ubiquitin onto nuclear cGAS. A cryo-electron microscopy structure of nucleosome-bound cGAS in a complex ....

Cytiva Akt , Lipofectamine Rnai , Jackson Immunoresearch , Microplates Perkin Elmer , Q Exactive Orbitrap , Phenoplate Perkinelmer , Proteome Software , Cell Signaling Technology , Electron Microscopy Sciences , Image Lab Software , Ge Healthcare Life Sciences , Carl Zeiss , Cell Biologics , Thermo Fisher Scientific , Supplementary Table , Thermo Fisher , Select Human Ubiquitin , Life Sciences , Perkin Elmer , Life Technologies , Omplete Protease Inhibitor Cocktail , Alexa Fluor , Santa Cruz , Click It Edu Imaging Kit , Mini Kit , Trans Blot Turbo ,

ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims

ROM1 is redundant to PRPH2 as a molecular building block of photoreceptor disc rims
elifesciences.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from elifesciences.org Daily Mail and Mail on Sunday newspapers.

United States , San Diego , United Kingdom , Baden Wüberg , Bio Rad Chemidoc , Ted Pella , University Of Houston , Association For Research , Roderickr Mcinnes Mcgill University , Image Lab , Electron Microscopy Sciences , Beckman Coulter , Image Lab Software , Supplementary Table , Institutional Animal Care , Use Committee , Roderickr Mcinnes , Mcgill University , Buffalo Grove , For Supplementary Figure , Bromophenol Blue , Blocking Buffer , Intelligent Imaging Innovations , Bio Rad Protein Assay ,

Channel Function of Polycystin-2 in the Endoplasmic Reticulum Protects against Autosomal Dominant Polycystic Kidney Disease

Significance Statement
Mutations of PKD2 encoding polycystin-2 cause autosomal dominant polycysti ....

United States , Antifade Mountant , Los Angeles , Viagen Direct , Gia Voeltz Addgene , Feng Zhang Addgene , Enzo Biochem , Metafluor Imaging Software Molecular Device , National Institute Of Diabetes , Care Of Laboratory Animals , Drummond Scientific Co , Baltimore Polycystic Kidney Disease Research , Jianjie Ma Ohio State University Medical Center , Score Center , John University , University Of Iowa Animal Care , Clinical Core Center , Alan Yu University Of Kansas Medical Center , Image Lab Software Bio Rad , National Institute , Kidney Diseases , Clinical Core , Modified Eagle Medium , Pen Strep , Site Directed Mutagenesis , Kansas Medical Center ,

Frontiers | Notch2 Increases the Resistance to Venetoclax-Induced Apoptosis in Chronic Lymphocytic Leukemia B Cells by Inducing Mcl-1

Chronic lymphocytic leukemia (CLL) has experienced a clinical revolution thanks to the discovery of crucial pathogenetic mechanisms. CLL is still an incurable disease due to intrinsic or acquired resistance of the leukemic clone. Venetoclax is a Bcl-2 inhibitor with a marked activity in CLL, but emerging patterns of resistance are being described. We hypothesize that intrinsic features of CLL cells may contribute to drive mechanisms of resistance to venetoclax. We analyzed the expression of IRF4, Notch2 and Mcl-1 in a cohort of CLL patients. We evaluated CLL cells viability after genetic and pharmaceutical modulation of Notch2 expression in patients harboring trisomy 12. We tested venetoclax in trisomy 12 CLL cells either silenced or not for Notch2 expression or in combination with an inhibitor of Mcl-1, AMG-176. Trisomy 12 CLL cells were characterized by low expression of IRF4 associated with high levels of Notch2 and Mcl-1. Notch2 and Mcl-1 expression determined protection of CLL cel ....

United States , Eteläuomen Läi , Menlo Park , Uppsala Lan , Landskapet Birkaland , Italy General , San Diego , Fondazione Cariplo , Ricerca Sul Cancro , Associazione Italiana , Progetto Eccellenza , Stefania Benatti , Fondazione Umberto Veronesi , Nucleofector Lonza , Comitato Etico Provinciale , Gilead Sciences , Becton Dickinson , Associates With Nodal Presentation , Image Lab Software , Flowjo Software , Division Of Hematology Modena , Deletion Accelerates Chronic Lymphocytic Leukemia Development , Late Germinal Center Differentiation , Subsequent Development Of Lymphadenopathy , Ge Healthcare , Tumor Protein ,

Alpelisib administration reduced lymphatic malformations in a mouse model and in patients

Alpelisib administration reduced lymphatic malformations in a mouse model and in patients
science.org - get the latest breaking news, showbiz & celebrity photos, sport news & rumours, viral videos and top stories from science.org Daily Mail and Mail on Sunday newspapers.

France General , Necker Enfants Malades , Amnis Imagestream , Klippel Trenaunay , Miltenyi Gmb , Image Lab Software Bio Rad Laboratories , Linstitut National De La Sant , Centre National De La Recherche Scientifique , Rp Cell Signaling Technology , Cell Signaling Technology , Jackson Laboratory , Fresenius Medical Care , S Ortega Spanish National Cancer Research Center , Representativep S , Intradermal Evans , Spanish National Cancer Research Center , Enseignement Sup , Alexa Fluor , Thermo Fisher Scientific , Image Lab Software , Bio Rad Laboratories , Applied Biosystems , Miltenyi Gmbh , Necker Enfants , Des Produits De Sant , Adverse Events ,