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     

Syndecan-4 Phosphorylation Is a Control Point for Integrin Recycling

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Highlights? c-Src phosphorylates syndecan-4 in response to extracellular stimuli ? Syndecan-4 phosphorylation and engagement regulate Arf6 activity ? Syndecan-4-mediated Arf6 activity regulates differential integrin recycling ? Syndecan-4-mediated integrin recycling controls FA dynamics and cell migration     

Structure of Phosphorylated SF1 Bound to U2AF65 in an Essential Splicing Factor Complex

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Highlights? Splicing factor SF1 phosphorylation on a conserved SPSP motif is required in vivo ? SPSP phosphorylation (P) induces local folding within an SF1/U2AF⁶⁵ interface ? Phosphorylation promotes an acutely bent (P)SF1/U2AF⁶⁵/RNA conformation     

HIV Nef,Paxillin, and Pak1/2 Regulate Activation and Secretion of TACE/ADAM10 Proteases

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Highlights? HIV-Nef translocates activated TACE/ADAM17 into extracellular vesicles (EVs) ? The mechanism is initiated by interaction of Eed and paxillin with TACE ? Translocation of TACE into EVs is regulated by Pak2 ? Melanoma cells activate the same mechanism to upload activated ADAM10 into EVs     

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     

Regulation of the CRL4Cdt2 Ubiquitin Ligase and Cell-Cycle Exit by the SCFFbxo11 Ubiquitin Ligase

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Highlights? FBXO11 targets CDT2, a CRL4 substrate receptor, for proteasomal degradation ? CDK-mediated phosphorylation of CDT2 degron inhibits recognition by FBXO11 ? FBXO11-mediated degradation of CDT2 controls the timing of cell-cycle exit ? FBXO11-CDT2 functional interaction is evolutionary conserved from worms to humans     

The Structure of the Tiam1 PDZ Domain/ Phospho-Syndecan1 Complex Reveals a Ligand Conformation that Modulates Protein Dynamics

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Highlights? The Tiam1 PDZ domain preferentially binds a subset of syndecan (SDC) proteins ? The PDZ domain/phospho-SDC1 structure reveals a phosphoryl binding pocket ? Ligand specificity and phosphorylation regulate PDZ/SDC interactions and signaling ? Tiam1 PDZ domain dynamics are ligand-dependent and regulated by phosphorylation     

SIP1 Mediates Cell-Fate Decisions between Neuroectoderm and Mesendoderm in Human Pluripotent Stem Cells

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Highlights? Smad-interacting protein 1 (SIP1) regulates hESC differentiation ? SIP1 upregulation promotes neuroectodermal differentiation ? SIP1 inhibits mesendodermal and endodermal differentiation ? SMAD2/3 and NANOG/OCT4/SOX2 cooperatively regulate SIP1 expression     

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     

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     

Kinetic Competition between RNA Polymerase II and Sen1-Dependent Transcription Termination

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Highlights? Fast Pol II elongation rate leads to Sen1-dependent termination defects ? Deletion of Rrp6 reveals a noncoding RNA termination window sensitive to Pol II rate ? Slow Pol II rate promotes earlier Sen1 termination events, rescues sen1 defects ? Fast Pol II rate promotes later Sen1 termination events, worsens sen1 defects     

The Retroviral Restriction Ability of SAMHD1, but Not Its Deoxynucleotide Triphosphohydrolase Activity,Is Regulated by Phosphorylation

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Highlights? SAMHD1 only exhibits antiviral activity when expressed in noncycling cells ? SAMHD1 is unphosphorylated in noncycling cells ? Reverse genetics revealed that phosphorylated SAMHD1 is repressive for restriction ? SAMHD1 phosphorylation regulates restriction, but not the cellular levels of dNTPs     

O-GlcNAc Signaling Entrains the Circadian Clock by Inhibiting BMAL1/CLOCK Ubiquitination

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Highlights? The hexosamine/O-GlcNAc pathway regulates cellular clock oscillation ? OGT promotes expression of BMAL1/CLOCK target genes in cultured cells and liver ? Rhythmic O-GlcNAcylation stabilizes BMAL1 and CLOCK by inhibiting their ubiquitination ? Hepatic manipulation of OGT perturbs the diurnal rhythm of glucose homeostasis     

Replacement of Oct4 by Tet1 during iPSC Induction Reveals an Important Role of DNA Methylation and Hydroxymethylation in Reprogramming

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Highlights? Tet1 facilitates iPSC induction by promoting Oct4 demethylation and reactivation ? Tet1 can replace Oct4 to generate fully pluripotent TSKM iPSCs ? Both 5mC and 5hmC increase on the genome during TSKM 2° reprogramming ? 5hmC promotes the demethylation of pluripotency genes during reprogramming     

Design of a Phosphorylatable PDZ Domain with Peptide-Specific Affinity Changes

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Highlights? Successful design of phosphorylation sites into a globular protein ? Redesigned PDZ domain phosphorylation is associated with local destabilization ? Phosphorylation switches peptide binding function ? Phosphorylation switches peptide recognition specificity     

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     

hnRNP A1 proofreads 3' splice site recognition by U2AF

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Highlights? hnRNP A1 displaces U2AF from uridine-rich RNAs not followed by a 3′ splice site AG ? A 3′ splice site AG allows formation of a ternary complex with hnRNP A1 and U2AF ? AG proofreading requires U2AF35 and the glycine-rich domain of hnRNP A1 ? hnRNP A1-mediated proofreading influences U2 snRNP recruitment     

IKKε regulates cell elongation through recycling endosome shuttling

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Highlights? Recycling endosomes shuttle along the proximal-distal axis of growing bristles ? IKK? locally antagonizes Rab11 effector Nuf at the bristle tip by phosphorylation ? Nuf-endosome pathway is independent of actin cytoskeleton or DIAP1-caspase pathway ? Mammalian IKK-related kinases antagonize Rab11-FIP3 through phosphorylation     

Noncanonical Role of the 9-1-1 Clamp in the Error-Free DNA Damage Tolerance Pathway

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Highlights? 9-1-1 and Exo1 are components of the error-free RAD6 pathway ? 9-1-1 promotes postreplicative template switching ? Polyubiquitylated PCNA and 9-1-1 cooperate in the error-free RAD6 pathway ? 9-1-1’s role in the error-free RAD6 pathway is uncoupled from checkpoint functions     

Two Deubiquitylases Act on Mitofusin and Regulate Mitochondrial Fusion along Independent Pathways

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Highlights? Mitochondrial fusion is regulated by independent ubiquitylation pathways ? The deubiquitylase Ubp2 promotes fusion, whereas Ubp12 inhibits fusion events ? Self-assembly and ubiquitylation cooperatively enable mitochondrial fusion ? Yeast mitofusin is sequentially ubiquitylated