Deubiquitination of NLRP3 by BRCC3 Critically Regulates Inflammasome Activity

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Highlights? Inhibition of deubiquitination blocks inflammasome activation ? Inhibition of deubiquitination induces NLRP3 polyubiquitination ? Deubiquitination of NLRP3 regulates the activation of inflammasome ? The deubiquitinating enzyme BRCC3 deubiquitinates the LRR domain of NLRP3     

A dynamic complex of signaling proteins uses polar localization to regulate cell-fate asymmetry in Caulobacter crescentus

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Highlights? DivL, an unorthodox kinase, promotes activation of the master kinase CckA ? Phosphorylated DivK binds directly to DivL to block the activation of CckA ? Cell cycle and cellular asymmetry are driven by changes in DivK phosphorylation ? Full activation of CckA depends on polar localization with a DivK phosphatase, PleC     

Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I

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Highlights? Crystallographic structure of RIG-I with 5′ triphosphorylated RNA duplex and ADP ? Solution biophysical analysis of ATP-dependent RIG-I conformational change ? The structural basis for ATP-stimulated RIG-I activation     

Towards a structural understanding of PARP1 activation and related signalling ADP-ribosyl-transferases

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Highlights? PARP1 recognizes DNA strand breaks through substrate-assisted dimerization. ? PARP1 ZFIII and WGR domains link DNA break recognition to enzyme activation. ? Tankyrase-dependent PARylation regulates Wnt signalling and Cherubism syndrome.     

Homeodomain-interacting protein kinase regulates yorkie activity to promote tissue growth

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Highlights? Hipk induces tissues overgrowth and leads to activation of Yki target genes ? Hipk is required for activity of hyperactive Yki ? Hipk kinase function is essential to promote Yki target genes     

Inactivation of BAD by IKK Inhibits TNFα-Induced Apoptosis Independently of NF-κB Activation

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Highlights? IKK can inhibit TNFα-induced apoptosis independently of NF-κB activation ? Inhibition of BAD constitutes the NF-κB-independent antiapoptotic axis of IKK ? IKK phosphorylates BAD at Ser26 and primes it for inactivation ? BAD inactivation coordinates with NF-κB activation to suppress TNFα-induced apoptosis     

β-Catenin-Driven Binary Fate Specification Segregates Germ Layers in Ascidian Embryos

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Highlights? β-catenin nuclear asymmetry after animal-vegetal-oriented cell divisions ? β-catenin nuclear asymmetry drives binary cell fate choices ? Combinatorial codes of nuclear β-catenin activation segregate ascidian germ layers ? Nuclear β-catenin ON-to-OFF activity is required for marginal mesoderm formation     

Division-coupled astrocytic differentiation and age-related depletion of neural stem cells in the adult hippocampus

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Highlights? The neural stem cell pool declines over time during aging ? Neural stem cell activation prompts rapid asymmetric divisions ? After undergoing division, neural stem cells differentiate into astrocytes     

Imparting Regenerative Capacity to Limbs by Progenitor Cell Transplantation

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Highlights? Transplantation of limb progenitor cells promotes multiple digit regenerates ? Wnt/β-catenin activation is required to stimulate adult frog limb regeneration ? Growth factors promote cell survival and growth and give pattern information ? Regeneration-incompetent host limb cells contribute to the regenerated limbs     

Conserved and Divergent Roles of FGF Signaling in Mouse Epiblast Stem Cells and Human Embryonic Stem Cells

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Highlights? Nanog is a direct target of Activin and SMAD2/3 but not FGF-ERK in EpiSCs ? FGF signaling inhibits neuroectodermal commitment of EpiSCs and hESCs ? FGF inhibition relieves Klf2 repression and reverts EpiSCs to an ESC-like state ? mESCs transition to an EpiSC-like state with LIF inhibition and FGF activation     

Loss of Scar/WAVE Complex Promotes N-WASP- and FAK-Dependent Invasion

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Highlights? Arp2/3 complex drives epithelial cell invasion in the absence of WRC ? Loss of WRC promotes N-WASP-dependent invasion and degradative focal adhesions ? Loss of WRC promotes FAK activation and enhances anchorage-independent growth ? WRC suppresses cell transformation and tumor formation     

Host cell autophagy activated by antibiotics is required for their effective antimycobacterial drug action

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Highlights? Antimycobacterial antibiotics activate autophagy in Mtb-infected host cells ? Autophagy activation depends on cellular and mitochondrial reactive oxygen species ? Host cell autophagy is essential for antimycobacterial drug action in infected macrophages and flies ? Antibiotic-induced autophagy dampened proinflammatory responses in infected macrophages     

Mechanism for KRIT1 Release of ICAP1-Mediated Suppression of Integrin Activation

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Highlights? Cocrystal structure of KRIT1 with ICAP1 shows a bidentate interaction interface ? Cocrystal structure of ICAP1 with integrin β1 shows a PTB-peptide interaction ? KRIT1 antagonizes ICAP1-modulated integrin activation by the bidentate interaction ? KRIT1 contains a previously undescribed N-terminal Nudix domain     

Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCι in complex with a substrate peptide from Par-3

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Highlights? The 3D structure of PKCι in complex with a peptide from Par-3 is determined ? PKCι does not need phosphorylation of Thr402 in its activation loop for its activity ? aPKCs do not need a priming kinase for their activations ? The PKCι/Par-3 structure reveals a unique substrate recognition patterns for aPKCs     

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     

An OsCEBiP/OsCERK1-OsRacGEF1-OsRac1 Module Is an Essential Early Component of Chitin-Induced Rice Immunity

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Highlights? Chitin induces rapid activation of the rice small GTPase OsRac1 at the plasma membrane ? OsRacGEF1 interacts with and acts as a guanine nucleotide exchange factor for OsRac1 ? In response to chitin, OsRacGEF1 is activated via phosphorylation by OsCERK1 ? OsRacGEF1 is required for chitin-driven immunity and resistance to rice blast fungus     

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     

A DNA-Damage Selective Role for BRCA1 E3 Ligase in Claspin Ubiquitylation,CHK1 Activation,and DNA Repair

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Highlights? BRCA1 E3 ligase activity is essential for a subset of DNA damage responses ? BRCA1 V26A mutant cells are sensitive to topoisomerase inhibitors but not mitomycin C ? BRCA1 selectively ubiquitylates claspin after topoisomerase inhibition ? BRCA1 E3 ligase inactivation selectively impairs CHK1 activation     

Dynamin 2 Potentiates Invasive Migration of Pancreatic Tumor Cells through Stabilization of the Rac1 GEF Vav1

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Highlights? Dyn2 promotes lamellipodia formation and pancreatic tumor cell migration ? Direct binding between Dyn2 and Vav1 promotes Rac1 activation and migration ? Dyn2 binding protects Vav1 from degradation by the lysosome ? Vav1 is targeted for degradation through an interaction with Hsc70     

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