AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth In Vivo

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Highlights? Loss of AMPKα1 cooperates with the Myc oncogene to accelerate lymphomagenesis ? AMPKα dysfunction enhances aerobic glycolysis (Warburg effect) ? Inhibiting HIF-1α reverses the metabolic effects of AMPKα loss ? HIF-1α mediates the growth advantage of tumors with reduced AMPK signaling     

Snx3 Regulates Recycling of the Transferrin Receptor and Iron Assimilation

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Highlights? Snx3 is highly expressed in vertebrate hematopoietic tissues ? Silencing of Snx3 results in anemia and hemoglobin defects in vertebrates ? Snx3 and Vps35 physically interact with Tfrc ? Snx3 is required for endosomal recycling of Tf-Tfrc complex     

Metabolic Stress Controls mTORC1 Lysosomal Localization and Dimerization by Regulating the TTT-RUVBL1/2 Complex

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Highlights? Glucose and glutamine feed back to promote mTORC1 signaling through ATP production ? Energetic stress prevents mTOR lysosomal localization independently of AMPK and Rag ? ATP-dependent TTT-RUVBL complex is disassembled and repressed by energetic stress ? TTT-RUVBL is required for mTORC1 functional assembly and lysosomal localization     

Human IL-34 and CSF-1 Establish Structurally Similar Extracellular Assemblies with Their Common Hematopoietic Receptor

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Highlights? Structural insights into the complete extracellular human IL-34:CSF-1R complex ? The C-terminal tail of hIL-34 is flexible and heavily O-linked glycosylated ? Inclusion of N-linked glycans drastically improves fitting of models to SAXS data ? Consensus principles for hCSF-1R activation by its two distinct cytokine ligands     

Metabolic Regulation by the Mitochondrial Phosphatase PTPMT1 Is Required for Hematopoietic Stem Cell Differentiation

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Highlights? PTPMT1 depletion causes cell cycle delay and differentiation block in HSCs ? The HSC pool in PTPMT1 knockout mice is drastically (～40-fold) expanded ? Mitochondrial metabolism is altered and AMPK is highly activated in knockout HSCs ? PTPMT1 PIP substrates directly enhance fatty-acid-induced activation of UCP2     

Inhibition of protein phosphatase 2A activity by PI3Kγ regulates β-adrenergic receptor function

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Highlights? PI3Kγ inhibits βAR resensitization by regulating PP2A activity ? PI3Kγ inhibits PP2A activity by phosphorylating I2PP2A on Serine 9 and 93 ? Phosphorylation of I2PP2A leads to its agonist-mediated interaction with PP2A ? siRNA-targeted depletion of I2PP2A results in βAR resensitization     

A microRNA miR-34a-Regulated Bimodal Switch Targets Notch in Colon Cancer Stem Cells

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Highlights? miR-34a regulates colon cancer stem cell asymmetric division ? miR-34a generates a sharp threshold response ? miR-34a converts Notch signaling into a toggle switch ? Binary Notch levels specify self-renewal versus differentiation     

Imbalance between Neutrophil Elastase and its Inhibitor α1-Antitrypsin in Obesity Alters Insulin Sensitivity,Inflammation, and Energy Expenditure

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Highlights? Obese men and mice have decreased serum A1AT levels and increased NE activity ? Neutrophil infiltration and NE deposition occur in adipose tissue from HFD-fed mice ? NE^?/? and A1AT Tg mice have reduced HFD-induced insulin resistance and inflammation ? NE deletion increases AMPK signaling and fatty acid oxidation in liver and BAT     

Structural Mechanism of CCM3 Heterodimerization with GCKIII Kinases

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Highlights? Crystal structure of CCM3-MST4 heterodimeric complex ? Structural mechanism driving CCM3-GCKIII heterodimerization ? Conformational changes required for CCM3-GCKIII heterodimerization ? Synergistic effects of CCM3-MST4 complex on cell proliferation and migration     

Dynamic Interaction between Sigma-1 Receptor and Kv1.2 Shapes Neuronal and Behavioral Responses to Cocaine

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Highlights? Sig-1R activity enhances sensitivity to cocaine by decreasing accumbal firing ? Cocaine decreases accumbal firing via Sig-1R-dependent increase of Kv1.2 current ? The Sig-1R forms a complex with Kv1.2 channel in the nucleus accumbens shell ? Cocaine triggers a long-lasting upregulation of the Sig-1R-Kv1.2 channel complex     

Structure and mechanism of the CMR complex for CRISPR-mediated antiviral immunity

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Highlights? EM structure of the CMR complex for viral RNA degradation has been determined ? The crRNA content of CMR has been analyzed by deep sequencing ? Target RNA cleavage by CMR is sequence dependent     

Cyclical Action of the WASH Complex: FAM21 and Capping Protein Drive WASH Recycling,Not Initial Recruitment

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Highlights? Dictyostelium WASH complex neutralizes lysosomes, then is recycled in small vesicles ? FAM21 is required at a different step than the other four WASH complex subunits ? Mutants in FAM21 can make actin on vesicles but cannot recycle WASH complex after use ? WASH complex is recycled coupling between actin, capping protein, and FAM21     

Adaptation of Aminoacyl-tRNA Synthetase Catalytic Core to Carrier Protein Aminoacylation

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Highlights? The crystal structure of the aa:CP ligase in complex with carrier protein was solved ? The interaction relies on the idiosyncratic α-helix of the aa:CP ligase ? The complex represents a unique mode of carrier protein recognition and binding ? The mechanism of amino acid attachment to carrier protein is discussed     

Fibronectin Regulates Wnt7a Signaling and Satellite Cell Expansion

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Highlights? Fzd7 and Sdc4 form a coreceptor complex in satellite cells ? FN stimulates Wnt7a activity through the Fzd7/Sdc4 coreceptor complex ? Activating satellite cells remodel their niche with FN ? FN regulates the satellite cell pool during muscle regeneration     

HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity

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Highlights? C. elegans DAF-2 insulin-like signaling negatively regulates HSF-1 activity ? DDL-1 and DDL-2 are negative regulators of HSF-1 ? Formation of a complex containing DDL-1/2 and HSF-1 inhibits HSF-1 activity ? DAF-2 signaling promotes DHIC formation by inhibiting DDL-1 phosphorylation     

Molecular and structural basis of ESCRT-III recruitment to membranes during archaeal cell division

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Highlights? A conserved protein, CdvA, recruits ESCRT-III to membranes during cell division ? Recruitment is mediated by a peptide-winged helix domain interaction ? We have determined the structure of this complex ? CdvA and a single ESCRT-III protein can drive membrane deformation in vitro     

Selective Chemical Crosslinking Reveals a Cep57-Cep63-Cep152 Centrosomal Complex

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Highlights? Selective chemical crosslinking identifies novel protein-protein interactions ? Superresolution microcopy defines the localization of centrosomal proteins ? Cep57, Cep63, and Cep152 form a ring-like centrosomal complex