Post-translational modifications articles within Nature Communications

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  • Article
    | Open Access

    Deciphering patterns of histone modifications that modulate chromatin structure and function is important, but remains challenging. Here the authors describe a method to uncover patterns of site-specific histone acetylation by deconvolution of overlapping peptide isomer mass spectra.

    • Nebiyu Abshiru
    • , Olivier Caron-Lizotte
    •  & Pierre Thibault

  • Article
    | Open Access

    A variety of signals have been reported to either activate or inhibit the Hippo kinase cascade. Here, Meng et al. show that mitogen activated protein kinase kinase kinase kinase (MAP4K) family members function in parallel to and are partially redundant with MST1/2 in regulating LATS in response to upstream signals.

    • Zhipeng Meng
    • , Toshiro Moroishi
    •  & Kun-Liang Guan

  • Article
    | Open Access

    The pentose phosphate pathway is aberrantly activated in cancer cells but the mechanism is unclear. Here, the authors show that G6PD, the rate-limiting enzyme in the pathway, is post-translationally modified with a sugar moiety under hypoxic conditions leading to increased production of precursors for macromolecular synthesis and antioxidants.

    • Xiongjian Rao
    • , Xiaotao Duan
    •  & Wen Yi

  • Article
    | Open Access

    Bub1 kinase phosphorylates histone H2A-T120 at the centromere to recruit shugoshin proteins and promote sister chromatid cohesion during mitosis. Here the authors show that Bub1 autophosphorylation on T589 influences Bub1 dynamics at the kinetochore and restricts H2A-T120 phosphorylation to centromeres.

    • Adeel Asghar
    • , Audrey Lajeunesse
    •  & Sabine Elowe

  • Article
    | Open Access

    Mice lacking RIIβ, a regulatory subunit of protein kinase A, are lean and resistant to diet-induced obesity. Here, the authors show that RIIβ regulates leptin sensitivity, acting as a physiological brake on leptin responsiveness and the duration of leptin signalling in the hypothalamus.

    • Linghai Yang
    •  & G. Stanley McKnight

  • Article
    | Open Access

    In response to brain injury, microglia extend processes to isolate the lesion. Here Choi et al. show that microglia expressing a pathogenic mutation in the Parkinson’s disease-associated LRRK2 gene show reduced motility and delayed lesion isolation in vitro and in vivodue to attenuated focal adhesion kinase activity.

    • Insup Choi
    • , Beomsue Kim
    •  & Eun-Hye Joe

  • Article
    | Open Access

    Glucocorticoid-induced TNFR-related protein (GITR), a costimulatory protein expressed by T cells, has immunostimulatory effect but the underlying mechanism is not clear. Here the authors show that GITR ligation inhibits the induction of Foxp3 expression and diverts CD4 T cells towards Th9 differentiation instead of iTreg.

    • Xiang Xiao
    • , Xiaomin Shi
    •  & Xian Chang Li

  • Article
    | Open Access

    Phosphoproteomics can offer significant insight into cell signalling and how signalling is modified in response to perturbations. Here the authors develop a new tool for the analysis of high-content phosphoproteomics in the context of kinase/phosphatase-substrate knowledge, which is used to train logic models.

    • Camille D. A. Terfve
    • , Edmund H. Wilkes
    •  & Julio Saez-Rodriguez

  • Article
    | Open Access

    The target of rapamycin complex 1 (TORC1) pathway couples nutrient availability with cell growth and division by destabilizing the cyclin-dependent kinase (CDK) inhibitor Sic1. Here the authors show that TORC1 downregulation leads to stabilization of Sic1 via phosphorylation by the MAP kinase Mpk1 and inhibition of dephosphorylation via the greatwall kinase pathway.

    • Marta Moreno-Torres
    • , Malika Jaquenoud
    •  & Claudio De Virgilio

  • Article
    | Open Access

    The effects of protein phosphorylation, a common post-translational modification, are difficult to study using recombinant proteins. Here the authors use genomically engineered E. colito enhance translation systems that express phosphor-serine containing proteins, and use these systems to produce phosphorylated MEK1 kinase.

    • Natasha L. Pirman
    • , Karl W. Barber
    •  & Jesse Rinehart

  • Article
    | Open Access

    The potassium-chloride co-transporter, KCC2 is an essential component in maintaining a gradient for chloride ions in neurons. Here Stodberg and colleagues identify loss-of-function mutations in the encoding geneSLC12A5, which impair normal synaptic function associated with early-onset epilepsy.

    • Tommy Stödberg
    • , Amy McTague
    •  & Manju A. Kurian

  • Article
    | Open Access

    Synaptic plasticity is mediated by the dynamic localization of proteins at synapses, which is partly controlled via palmitoylation of synaptic proteins. Here, the authors show how neuronal activity regulates the palmitoylation reaction through the translocation of the palmitoyl-acyl transferase DHHC5.

    • G. Stefano Brigidi
    • , Brendan Santyr
    •  & Shernaz X. Bamji

  • Article
    | Open Access

    Cells respond to increasing concentrations of EGF by altering the balance between EGFR phosphorylation and ubiquitination. Here the authors show that the establishment of an EGFR signaling threshold requires both a multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR.

    • Fabrizio Capuani
    • , Alexia Conte
    •  & Andrea Ciliberto

  • Article
    | Open Access

    Endothelial cell activation by inflammation requires extracellular ATP release. Here the authors show that TNF-α induces Src-family kinase-dependent ATP release by Pannexin1 channels in endothelial cells, and that Pannexin1 is required for leukocyte adhesion and emigration into the inflamed tissue.

    • Alexander W. Lohman
    • , Igor L. Leskov
    •  & Brant E. Isakson

  • Article
    | Open Access

    Changes in protein–protein interactions result in changes to cellular phenotype. Here the authors use crosslinking mass spectrometry to derive a quantitative protein interaction network in drug-sensitive and -resistant HeLa cells, and uncover a chemoresistant ‘edgotype’.

    • Juan D. Chavez
    • , Devin K. Schweppe
    •  & James E. Bruce

  • Article
    | Open Access

    The level of chromatin condensation and gene expression is believed to be inversely correlated. Here the authors show that the transcriptionally silent telomere regions are flanked by highly condensed chromatin, and are less condensed than euchromatin in the interphase of Schizosaccharomyces pombe.

    • Atsushi Matsuda
    • , Yuji Chikashige
    •  & Yasushi Hiraoka

  • Article
    | Open Access

    TGF-ß and IL-6 are the essential cytokines for mediating the differentiation of IL-17-producing CD4+ T helper cells (TH17). Here, Yoon et al. provide more insights into this process and describe the opposing roles of TGFß-signalling intermediates Smad2 and Smad3 as STAT3 cofactors in Th17 differentiation.

    • Jeong-Hwan Yoon
    • , Katsuko Sudo
    •  & Mizuko Mamura

  • Article
    | Open Access

    Mutations and post-translational modifications of the PI3K/AKT pathway inhibitor PTEN are a feature of many cancers, but these have not been associated with cervical cancer. Here, the authors identify a PI3K/AKT-mediated ubiquitination degradation pathway of PTEN that occurs in patients with cervical cancer.

    • Min-Sik Lee
    • , Man-Hyung Jeong
    •  & Jaewhan Song

  • Article
    | Open Access

    N-terminal acetylation is a common protein modification in eukaryotes. Here the authors show that in Arabidopsis, N-terminal acetylation is decreased by drought stress, that abundance of an N-terminal acetyltransferase is reduced by abscisic acid and that constitutive downregulation can confer drought resistance.

    • Eric Linster
    • , Iwona Stephan
    •  & Markus Wirtz

  • Article
    | Open Access

    Synapsins anchor synaptic vesicles (SVs) to the actin cytoskeleton to establish the reserve vesicle pool. Here Tanget al. show that SUMOylation of synapsin 1a enhances its interaction with SVs to promote efficient reclustering following stimulation, and a mutation linked to autism and epilepsy leads to defective SUMOylation.

    • Leo T. -H. Tang
    • , Tim J. Craig
    •  & Jeremy M. Henley

  • Article
    | Open Access

    9-O-Acetylation is one of the most common modifications of sialic acids, implicated in sialoglycan recognition and ganglioside biology. Here, the authors show that the key enzyme for the biosynthesis of 9-O-acetylated sialoglycans is CASD1, which uses CMP-activated sialic acid as acceptor substrate.

    • Anna-Maria T. Baumann
    • , Mark J. G. Bakkers
    •  & Martina Mühlenhoff

  • Article
    | Open Access

    Directed cell migration requires spatially regulated activity of GTPases Rac1 and RhoA. Here Cao et al. show that growth factor stimulation promotes phosphorylation of tensin-3 and phosphatase and tensin homologue (PTEN) and their association with PI 3-kinase and deleted in liver cancer 1 (DLC1) to regulate GTPase activity.

    • Xuan Cao
    • , Tomonori Kaneko
    •  & Shawn S. C. Li

  • Article
    | Open Access

    The EphA2 receptor tyrosine kinase is overexpressed in many cancers and is reported to be phosphorylated by Akt. Here, Zhou et al.show that RSK, rather than Akt, phosphorylates EphA2 on Ser-897, and this regulates cell migration and invasion of metastatic cancer cells.

    • Yue Zhou
    • , Naoki Yamada
    •  & Hiroaki Sakurai

  • Article
    | Open Access

    The SUMO-targeted ubiquitin ligase RNF111 promotes K63-linked ubiquitylation of SUMOylated XPC after DNA damage. Here the authors show that RNF111 is responsible for sequential XPC ubiquitylation, and RNF111-mediated ubiquitylation promotes the release of XPC from damaged DNA after NER initiation.

    • Loes van Cuijk
    • , Gijsbert J. van Belle
    •  & Jurgen A. Marteijn

  • Article
    | Open Access

    Grb2 is an adaptor protein that can exist as a dimer that dissociates on phosphorylation of Y160. Here, the authors show that only the monomeric protein is capable of activating mitogen-activated protein kinase signal transduction and hence control oncogenic outcome.

    • Zamal Ahmed
    • , Zahra Timsah
    •  & John E. Ladbury

  • Article |

    mTOR signalling regulates protein synthesis in response to changes in nutrient availability. Chang et al.demonstrate that mTOR can stimulate translation by promoting the shortening of mRNA 3′-untranslated regions, and that expression of ubiquitin ligases is selectively enhanced by this mechanism.

    • Jae-Woong Chang
    • , Wei Zhang
    •  & Jeongsik Yong

  • Article
    | Open Access

    Tryptic digestion of SUMOylated proteins generates large peptides, rendering proteomic characterisation of this post-translational modification particularly challenging unless mutant SUMO is used. Hendriks et al.present a method that allows the quantitative identification of wild-type SUMO sites.

    • Ivo A. Hendriks
    • , Rochelle C. D’Souza
    •  & Alfred C. O. Vertegaal

  • Article
    | Open Access

    Type III restriction–modification enzymes consists of two methylation and one or two restriction subunits. Here the authors report the structure of the full EcoP15I complex bound to DNA, which suggests mechanisms for ATP hydrolysis dependent diffusion along DNA and how a dimeric methyltransferase modifies only one DNA strand.

    • Yogesh K. Gupta
    • , Siu-Hong Chan
    •  & Aneel K. Aggarwal

  • Article
    | Open Access

    Proximity ligation assays are a sensitive method for detecting protein interactions, but require the addition of enzymes. Here the authors introduce proxHCR, an enzyme-free method of detecting interactions in close proximity by inducing a hybribization chain reaction (HCR) of fluorescently labelled oligonucleotides.

    • Björn Koos
    • , Gaëlle Cane
    •  & Ola Söderberg

  • Article
    | Open Access

    SUMOylation of the cardiac calcium pump SERCA2a affects its activity and promotes cardiomyocyte contractility. Here the authors identify a small molecule N106 that increases SERCA2 SUMOylation and improves heart function in mice, and propose a promising therapeutic strategy for treatment of heart failure.

    • Changwon Kho
    • , Ahyoung Lee
    •  & Roger J. Hajjar

  • Article |

    The mechanisms regulating lymphatic vessel development and function are still largely unknown. Here, the authors show that the protein kinase Cdk5 is required for lymphatic vessel development by regulating the activity of the transcription factor Foxc2 and its target genes.

    • Johanna Liebl
    • , Siwei Zhang
    •  & Stefan Zahler

  • Article
    | Open Access

    Beclin 1 is an essential autophagy effector, necessary to form the autophagosome. Here Sun et al. show that Beclin 1 acetylation regulated by p300 and SIRT1 inhibits autophagosome maturation, and mutation of the acetylation sites leads to tumour growth suppression in vivo.

    • Ting Sun
    • , Xuan Li
    •  & Xiao-Feng Zhu

  • Article
    | Open Access

    DNMT1 is a methyl-transferase involved in maintaining tissue-specific patterns of DNA methylation. Here the authors solve the structure of a DNMT1-USP7 complex and demonstrate the mechanism by which DNMT1 stability is regulated through acetylation by preventing association with the deubiquitinase USP7.

    • Jingdong Cheng
    • , Huirong Yang
    •  & Yanhui Xu

  • Article
    | Open Access

    Polypeptide GalNAc-transferases decorate proteins with dense arrays of O-glycans, which in the case of mucins are essential for their barrier functions. Here the authors present comprehensive structural studies that shed light on the molecular attributes that allow GalNAc-T2 to efficiently carry out dense O-glycosylation.

    • Erandi Lira-Navarrete
    • , Matilde de las Rivas
    •  & Ramon Hurtado-Guerrero

  • Article
    | Open Access

    Folate plays an essential role in dividing cells and is regulated by methionine adenosyltransferase (MAT), where a switch from MAT Iα to MAT IIα expression seems to promote liver cancer progression. Here the authors demonstrate that MAT IIα stability is regulated by acetylation and this regulation is important for tumour growth.

    • Hong-Bin Yang
    • , Ying-Ying Xu
    •  & Qun-Ying Lei

  • Article |

    dDsk2 is a conserved extraproteasomal ubiquitin receptor that targets ubiquitylated proteins for degradation. Here the authors report that dDsk2 regulates RNA polymerase II pausing by preventing H2Bub1 deubiquitylation, suggesting a nonproteolytic function of dDsk2.

    • Roman Kessler
    • , Johan Tisserand
    •  & Fernando Azorín

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