ESCs Require PRC2 to Direct the Successful Reprogramming of Differentiated Cells toward Pluripotency

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Highlights? Mouse pluripotent cells reprogram human B cells in heterokaryons ? ESCs lacking PRC1 or PRC2 cannot successfully reprogram ? Failure of PRC1/2-deficient ESCs to reprogram is functionally dominant ? PRC1/2 play a critical role in the chromatin reorganization required for reprogramming     

Sequence-Specific Transcription Factor NF-Y Displays Histone-like DNA Binding and H2B-like Ubiquitination

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Highlights? 3D structure of NF-Y/CCAAT shows close relationships to core histones H2A/H2B ? NF-YA displays a sequence-specific DNA minor groove-binding module ? Histone H2B and NF-YB share a functional posttranslational modification ? NF-Y binding and monoubiquitination are early events in gene activation     

Fbxl10/Kdm2b Recruits Polycomb Repressive Complex 1 to CpG Islands and Regulates H2A Ubiquitylation

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Highlights? Fbxl10 binds to most CpG islands in ESCs ? Fbxl10 recruits Nspc1 and Ring1B to CpG islands ? The Fbxl10, Nspc1, and Ring1B complex is required for H2A monoubiquitylation ? Fbxl10 is required for proper ESC differentiation     

The E3 Ligase Parkin Maintains Mitochondrial Integrity by Increasing Linear Ubiquitination of NEMO

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Highlights? The stress-protective prosurvival activity of parkin depends on NEMO ? Parkin binds to LUBAC and increases linear ubiquitination of NEMO ? OPA1 is upregulated via parkin/NEMO/NF-κB for maintaining mitochondrial integrity ? TNF-α signaling via NEMO/NF-κB is impaired in parkin-deficient cells     

An ERK-p38 Subnetwork Coordinates Host Cell Apoptosis and Necrosis during Coxsackievirus B3 Infection

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Highlights? Intracellular signaling predicts the fate of coxsackievirus B3 (CVB3)-infected cells ? p38 and ERK signaling pathways are tightly interconnected during CVB3 infection ? CVB3-induced apoptosis of cardiomyocytes is inhibited by ERK5 and ERK1/2 pathways ? CVB3 induces necrosis of cardiomyocytes via p38 activation     

Bax Exists in a Dynamic Equilibrium between the Cytosol and Mitochondria to Control Apoptotic Priming

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Highlights? Bax exists in equilibrium between the cytosol and mitochondria ? The retrotranslocation of Bax is independent of direct-activator BH3 proteins ? Changes in survival signaling modulate the dissociation rate of mitochondrial Bax ? Accumulation of Bax on mitochondria sensitizes cells to apoptosis     

Sculpting of DNA at Abasic Sites by DNA Glycosylase Homolog Mag2

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Highlights? Unflipped AP site stabilized by helix-hairpin-helix DNA glycosylase homolog Mag2 ? Nonenzymatic AP site recognition and DNA sculpting ? Sculpting of DNA conformation enhances substrate transfer between proteins     

Supernumerary centrosomes nucleate extra cilia and compromise primary cilium signaling

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Highlights? Supernumerary centrosomes nucleate cilia, resulting in superciliated cells (SCC) ? Ciliary proteins are reduced in concentration in SCC, compromising signaling ? Presence of extra cilia disrupts epithelial organization in 3D spheroid culture ? Extra cilia may contribute to disease phenotypes by disrupting signaling     

Dynamic Response Diversity of NFAT Isoforms in Individual Living Cells

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Highlights? Two isoforms of the NFAT proteins possess distinct and diverse dynamic responses ? NFAT4 shows fast, stochastic, and frequency-modulated bursts of nuclear localization ? NFAT1 shows a slow, continuous, and amplitude-modulated nuclear localization ? Dynamic diversity can endow cells with enhanced signal processing capabilities     

Inhibition of Mitochondrial Aconitase by Succination in Fumarate Hydratase Deficiency

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Highlights? Fumarate inhibits Aconitase2 activity via succination of critical cysteine residues ? Endogenous Aconitase2 is succinated and inhibited in FH-deficient cells ? Succination occurs in multiple proteins with roles in diverse cellular processes ? Succination can alter metabolism in FH-deficient cells     

Microautophagy of cytosolic proteins by late endosomes

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Highlights? Late endosomes take up cytosolic proteins through membrane invaginations ? Endosomal microautophagy (eMI) requires multivesicular body formation ? hsc70 mediates selective targeting of cytosolic proteins during eMI ? hsc70 binds to the endosomal membrane through its polybasic cluster     

Sox2 Cooperates with Inflammation-Mediated Stat3 Activation in the Malignant Transformation of Foregut Basal Progenitor Cells

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Highlights? Sox2+ve basal stem/progenitor cells self-renew and differentiate in vitro and in vivo ? Conditional Sox2 overexpression promotes the expansion of basal progenitor cells ? Sox2 cooperates with an inflammatory microenvironment to induce squamous cancer ? Sox2 and Stat3 together transform mouse and human esophageal progenitor cells     

A Network Model of the Molecular Organization of Chromatin in Drosophila

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Highlights? DamID identifies 42 previously unknown chromatin proteins ? Binding maps of new and known chromatin components yield a chromatin network model ? The network model predicts functions of most of the 42 new chromatin proteins ? The chromatin protein network is functionally compartmentalized     

Distinct and Overlapping Roles for AP-1 and GGAs Revealed by the “Knocksideways” System

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Highlights? AP-1 knocksideways depletes ～100 proteins from clathrin-coated vesicles (CCVs) ? GGA2 knocksideways mainly depletes hydrolases and their receptors ? GGA2 depends on AP-1 for incorporation into CCVs ? AP-1 acts as a linchpin for intracellular CCV formation and is bidirectional     

Crystallographic and NMR Evidence for Flexibility in Oligosaccharyltransferases and Its Catalytic Significance

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Highlights? OST transfers an oligosaccharide chain to the Asn-X-Ser/Thr sequons in proteins ? A plastic segment found in crystal structures underwent dynamic motions in solution ? An engineered disulfide bond that locked the conformation abolished the OST activity ? Dynamic sequon recognition is implicated in efficient cotranslational N-glycosylation     

Modeling Alzheimer’s Disease with iPSCs Reveals Stress Phenotypes Associated with Intracellular Aβ and Differential Drug Responsiveness

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Highlights? Familial and sporadic Alzheimer’s patient iPSC-derived neural cells were analyzed ? Intracellular Aβ oligomers accumulate in lines from some patients ? Aβ oligomer accumulation is associated with ER and oxidative stress ? DHA-alleviated ER and oxidative stresses improve cell viability     

Tracking Shallow Chemical Gradients by Actin-Driven Wandering of the Polarization Site

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Highlights? A wandering polarity site distributes growth in yeast cells responding to pheromone ? Wandering, but not polarity establishment, is actin dependent ? A mathematical model incorporating polarity and vesicle traffic exhibits wandering ? Blocking wandering impairs gradient tracking     

Protein Determinants of Meiotic DNA Break Hot Spots

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Highlights? DSB hot spots for meiotic recombination are specified by largely unknown mechanisms ? Linear element proteins, required for most DSBs, are highly enriched at hot spots ? These proteins, the first known global hot spot determinants, bind without DSB formation ? Hot spot determination by these proteins provides a paradigm for crossover control