Post-translational modifications articles within Nature Communications

Featured

  • Article
    | Open Access

    Histone modifications play important roles in gene transcription and cancer. Here the authors establish a role for the E3 ubiquitin ligase NEDD4 in modifying in a glucose-dependent manner the histone H3, thus regulating the expression of genes involved in tumorigenesis.

    • Xian Zhang
    • , Binkui Li
    •  & Hui-Kuan Lin
  • Article
    | Open Access

    Tyrosine kinase signalling in cancer cells promotes immune evasion. Here, the authors show that tyrosine kinases engage scaffold protein Shc1 to promote immunosuppression in breast cancer by simultaneously activating STAT3 immunosuppressive signals and impairing STAT1-driven anti-tumour immune responses.

    • Ryuhjin Ahn
    • , Valérie Sabourin
    •  & Josie Ursini-Siegel
  • Article
    | Open Access

    Parkin and PINK1 are involved in damaged mitochondria clearance; however the sequence of events of Parkin activation is not clear. Here, the authors show that binding to phospho-ubiquitin on mitochondria enables Parkin phosphorylation, which allows Repressor Element of Parkin removal, E3 ligase activation and mitophagy.

    • Matthew Y. Tang
    • , Marta Vranas
    •  & Edward A. Fon
  • Article
    | Open Access

    Gluconeogenesis is downregulated in hepatocellular carcinoma. Here, the authors show that nuclear receptor Nur77 acts as a tumour suppressor sustaining gluconeogenesis by enhancing phosphoenolpyruvate carboxykinase (PEPCK1) stability via regulating its interaction with the SUMO-conjugating enzyme Ubc9.

    • Xue-li Bian
    • , Hang-zi Chen
    •  & Qiao Wu
  • Article
    | Open Access

    Expanding the genetic code with unnatural amino acids in model organisms is a powerful tool for investigatingin vivocellular proteins and processes. Here the authors re-engineer the amber stop codon in laboratory mice to allow site-specific incorporation of unnatural amino acids in target proteins.

    • Songmi Han
    • , Aerin Yang
    •  & Hee-Sung Park
  • Article
    | Open Access

    Snail1 is a key factor controlling epithelial-to-mesenchymal transition and cancer metastasis. While the E3 ligases responsible for Snail1 ubiquitination and degradation have been defined, the deubiquitinating enzyme is unknown. Here Zhou and colleagues show that Dub3 stabilizes Snail1 by removing ubiquitin, thus impacting breast cancer cell metastasis.

    • Yadi Wu
    • , Yu Wang
    •  & Binhua P. Zhou
  • Article
    | Open Access

    Mitochondrial reactive oxygen species (ROS) promote necroptosis and the receptor interacting protein 1 (RIP1) is a key player in this form of cell death. Here, the authors show that cysteine residues in RIP1 sense ROS and oxidation of the cysteines triggers RIP1 autophosphorylation, which promotes functional necrosome formation.

    • Yingying Zhang
    • , Sheng Sean Su
    •  & Jiahuai Han
  • Article
    | Open Access

    Humans that reach high altitude soon after the first ascent show faster adaptation to hypoxia. Songet al. show that this adaptive response relies on decreased red blood cell uptake of plasma adenosine due to reduced levels of nucleoside transporter ENT1 resulting from coordinated adenosine generation by ectonucleotidase CD73 and activation of A2B receptors.

    • Anren Song
    • , Yujin Zhang
    •  & Yang Xia
  • Article
    | Open Access

    The transfer of ubiquitin (UB) to cellular targets is mediated sequentially by three groups of enzymes, UB activating enzyme (E1), UB conjugating enzyme (E2) and UB ligase (E3). Here the authors provide evidence that the two mammalian E1 enzymes, Uba1 and Uba6, exert biologically distinct functions.

    • Xianpeng Liu
    • , Bo Zhao
    •  & Hiroaki Kiyokawa
  • Article
    | Open Access

    Overexpression of SNAIL confers tumour cells with cancer stem-like characteristics associated with tumour progression. Here the authors show that inhibition of CDK4/6 blocks tumour metastasis in triple negative breast cancer by targeting DUB3 which in turns deubiquitinates and stabilises SNAIL1.

    • Tongzheng Liu
    • , Jia Yu
    •  & Zhenkun Lou
  • Article
    | Open Access

    The protein tyrosine kinase c-Src is a renowned proto-oncogene with pleiotropic effects. Here, the authors show that c-Src induces the metabolic reprogramming of cancer cells by phosphorylating hexokinases HK1 and HK2, which in turns lead to increased HK catalytic activity and consequent enhancement of glycolysis.

    • Jia Zhang
    • , Suili Wang
    •  & Qinxi Li
  • Article
    | Open Access

    Hypoxia-induced transcriptional responses mediated by HIF-1a are regulated through the ubiquitin-dependent pathway to control HIF-1a stability. Here the authors show that the deubiquitinase HAUSP modulates the stability of HIF-1a and K63-polyubiquitinated HAUSP serves as an anchor for HIF-1a-induced gene transcription.

    • Han-Tsang Wu
    • , Yi-Chih Kuo
    •  & Kou-Juey Wu
  • Article
    | Open Access

    Multivesicular bodies (MVB) are endosomal compartments that can either fuse with the plasma membrane for the secretion of exosomes, or fuse with the lysosome and be degraded along with their contents. Here, the authors show that ISGylation of the MVB protein TSG101 impairs exosome secretion and acts as a regulator of MVB fate.

    • Carolina Villarroya-Beltri
    • , Francesc Baixauli
    •  & Francisco Sánchez-Madrid
  • Article
    | Open Access

    GCN5 inhibits hepatic gluconeogenesis through acetylation of PGC-1α. Here the authors show that GCN5 also activates hepatic gluconeogenesis by acetylating histone H3K9, and that the affinity of GCN5 for its different substrates is regulated via phosphorylation at S275 by PKA in a CITED2-dependent manner.

    • Mashito Sakai
    • , Tomoko Tujimura-Hayakawa
    •  & Michihiro Matsumoto
  • Article
    | Open Access

    Translesion synthesis polymerase eta has a well characterized role in replicating past UV-induced DNA lesions and has recently been shown to act at difficult to replicate sequences. Here the authors show that its SUMOylation is required to recruit pol eta at the replication fork and to prevent under-replicated DNA.

    • Emmanuelle Despras
    • , Méghane Sittewelle
    •  & Patricia L Kannouche
  • Article
    | Open Access

    Protein kinase A (PKA) is a key mediator of cyclic AMP signalling. Here, Eccles et al. show that ARHGAP36 antagonizes PKA by acting as a kinase inhibitor and targeting the catalytic subunit for endolysosomal degradation, thus reducing sensitivity of cells to cAMP and promoting Hedgehog signalling.

    • Rebecca L. Eccles
    • , Maciej T. Czajkowski
    •  & Oliver Rocks
  • Article
    | Open Access

    The chaperone Hsp70 has a dual role, promoting both protein refolding and protein degradation. Seo and Park et al. show that Hsp70 acetylation enhances protein refolding after stress, and that subsequent deacetylation progressively promotes ubiquitin ligase binding and protein degradation.

    • Ji Hae Seo
    • , Ji-Hyeon Park
    •  & Kyu-Won Kim
  • Article
    | Open Access

    The kinetochore-bound motor CENP-E plays a critical role in chromosome alignment. Here, the authors show that NF-κB activating protein (NKAP) dynamically localises to kinetochores, is SUMOylated during mitosis, and this modification is required for NKAP to bind CENP-E and localise CENP-E to the kinetochore.

    • Teng Li
    • , Liang Chen
    •  & Qing Xia
  • Article
    | Open Access

    ADP-ribosylation is a reversible post-translational protein modification involved in many cellular processes. Here the authors describe a sensitive approach for the analysis of ADP-ribosylation sites under physiologic conditions and identify lysine residues as in vivotargets of ADP-ribosylation.

    • Rita Martello
    • , Mario Leutert
    •  & Michael L. Nielsen
  • Article
    | Open Access

    Chemical approaches to site-specifically ubiquitylate a target protein allow investigation of the biochemical effects of this modification, but they often destabilize the protein. Here, the authors report on a synthetic conjugation strategy that leads to protein ubiquitylation in non-denaturing conditions.

    • Caroline E. Weller
    • , Abhinav Dhall
    •  & Champak Chatterjee
  • Article
    | Open Access

    Protein phosphorylation mediates signalling and other important cellular processes, but the specific effect of cysteine phosphorylation is unclear. Here, the authors present a chemical strategy to selectively phosphorylate cysteine residues and a mass spectrometry approach to detect and characterize endogenous pCys sites.

    • Jordi Bertran-Vicente
    • , Martin Penkert
    •  & Christian P. R. Hackenberger
  • Article
    | Open Access

    Insulin receptor levels at the cell surface are reduced in insulin resistance, for reasons that are not fully understood. Here, the authors identify the E3 ubiquitin ligase MARCH1 as a direct regulator of basal insulin receptor surface levels and, therefore, insulin signalling.

    • Arvindhan Nagarajan
    • , Max C. Petersen
    •  & Narendra Wajapeyee
  • Article
    | Open Access

    The effect of the liver clock is modified by food entrainment via Bmal1/Clock core machinery. Here the authors show that insulin promotes postprandial Akt-dependent phosphorylation of Bmal1, resulting in association with 14-3-3 and Bmal1 shuttling out of the nucleus, thereby disrupting Bmal1 transcriptional effects on the clock.

    • Fabin Dang
    • , Xiujie Sun
    •  & Yi Liu
  • Article
    | Open Access

    Programmed Death ligand-1 (PD-L1) protein mediates immune suppression in cancer. Here, the authors show that in breast cancer, PD-L1 expression can be up regulated post-translationally by glycosylation, which in turn acts through inhibiting GSK3β-mediated PD-L1 degradation.

    • Chia-Wei Li
    • , Seung-Oe Lim
    •  & Mien-Chie Hung
  • Article
    | Open Access

    CYLD is a deubiquitinase known to act as a tumour suppressor in different models of carcinogenesis. Here, the authors show that CYLD suppresses carcinogen-induced tumorigenesis by deubiquitinating p53 and promoting its stabilization and activation in response to DNA damage.

    • Vanesa Fernández-Majada
    • , Patrick-Simon Welz
    •  & Manolis Pasparakis
  • Article
    | Open Access

    Regulators of the important ubiquitylation cascade are not well studied. Here, the authors report the crystal structure of a prenylated membrane-anchored ubiquitin-fold protein from Arabidopsisbound to an E2 protein and conclude that it is an example of selective activation between E2 enzymes.

    • Xiaolong Lu
    • , Konstantin R. Malley
    •  & Brian P. Downes
  • Article
    | Open Access

    The ‘genome guardian’ p53 has a well-established role in suppressing tumour development after DNA damage. Here the authors show that expression of the ubiquitin-like protein ISG15 is regulated by p53 which in turn is modified by ISG15 to enhance binding to target gene promoters.

    • Jong Ho Park
    • , Seung Wook Yang
    •  & Chin Ha Chung
  • Article
    | Open Access

    Gene expression is regulated by a range of mechanisms, including post-translational modifications such as phosphorylation. Here the authors present evidence for a feedback mechanism whereby hyperphosphorylation of UPF1 in response to delays in nonsense-mediated decay enhances recruitment of mRNA decay machinery.

    • Sébastien Durand
    • , Tobias M. Franks
    •  & Jens Lykke-Andersen
  • Article
    | Open Access

    In conditions of energy stress cells reduce transcription of ribosomal RNA (rRNA) to maintain cell survival. Here, the authors show that energy stress induces an AMPK-dependent phosphorylation of Sirt7, which promotes its ubiquitin-independent degradation by REGγ, resulting in the down-regulation of rRNA transcription and cell survival.

    • Lianhui Sun
    • , Guangjian Fan
    •  & Chuangui Wang
  • Article
    | Open Access

    Phosphorylation of L-type calcium CaV channels by protein kinase A is essential for several physiological events. Here, the authors show how this kinase regulates CaV1.4 activity, suggesting a general regulatory mechanism for all L-type calcium channels.

    • Lingjie Sang
    • , Ivy E. Dick
    •  & David T. Yue
  • Article
    | Open Access

    MicroRNAs are a widespread regulatory mechanism and are themselves extensively regulated. Here the authors show regulated miRNA biogenesis by the target mRNA, a layer of regulation that modulates miRNA levels dependent on target availability.

    • Mainak Bose
    •  & Suvendra N. Bhattacharyya
  • Article
    | Open Access

    Lysine hydroxylation of procollagen precursors by LH3 is required for collagen fibril crosslinking and stabilization. Here the authors show that the trafficking protein VIPAR is required for correct sorting of LH3 into post-Golgi collagen carriers and for correct collagen modification and structure.

    • Blerida Banushi
    • , Federico Forneris
    •  & Paul Gissen
  • Article
    | Open Access

    Claspin mediates the transmission of a replication-stress signal from ATR to Chk1 and is necessary for efficient fork progression. Here the authors demonstrate that the C-terminal acidic patch is important for this role due to its interaction with Cdc7.

    • Chi-Chun Yang
    • , Masahiro Suzuki
    •  & Hisao Masai
  • Article
    | Open Access

    Aurora B activation at the centromere is critical for faithful chromosome segregation in mammals. Here the authors show that Aurora B-mediated phosphorylation of histone H2AX at serine 121 is essential for Aurora B auto-activation circuitry at centromeres, ensuring proper chromosome segregation.

    • Midori Shimada
    • , Takahiro Goshima
    •  & Makoto Nakanishi
  • Article
    | Open Access

    Stress granules that form in response to stress contain translationally stalled mRNPs and play important roles in cellular homeostasis. Here the authors implicate SRSF3 neddylation as an important factor in the formation of stress granules in response to arsenite exposure.

    • Aravinth Kumar Jayabalan
    • , Anthony Sanchez
    •  & Takbum Ohn
  • Article
    | Open Access

    When the antibiotic erythromycin is bound to the ribosomal exit tunnel, ErmBL peptide translation stalls and allows translation of the downstream methyltransferase ErmB. Here the authors combine cryo-EM and molecular dynamics simulations to identify the underlying basis for the inhibition of peptide bond formation that results in ribosome stalling.

    • Stefan Arenz
    • , Lars V. Bock
    •  & Daniel N. Wilson
  • Article
    | Open Access

    The post-transcriptional 5-methylcytosine (m5C) modification occurs in a wide range of nuclear-encoded RNAs. Here the authors identify the mitochondrial tRNA-Met as a target for the m5C methyltransferase NSun3—found mutated in a mitochondrial disease patient—and link mitochondrial tRNA modifications with energy metabolism.

    • Lindsey Van Haute
    • , Sabine Dietmann
    •  & Michal Minczuk
  • Article
    | Open Access

    Altered function of the muscle LIM protein (MLP) causes dilated cardiomyopathy in mice and humans. Lange et al. explain the molecular role of MLP in the heart by showing that it affects the signalling complex at the intercalated discs of failing hearts that consists of PKCα, PLCβ1 and CARP by inhibiting PKCα auto-phosphorylation and function.

    • Stephan Lange
    • , Katja Gehmlich
    •  & Elisabeth Ehler
  • Article
    | Open Access

    Dysregulation of p62 has been implicated in tumorigenesis. Here, the authors show that p62 promotes hepatocellular carcinoma by reprogramming glucose and glutamine metabolism through Nrf2 and present a novel compound that can inhibit p62 action thus sensitizing cancer cells to chemotherapy.

    • Tetsuya Saito
    • , Yoshinobu Ichimura
    •  & Masaaki Komatsu
  • Article
    | Open Access

    While reversal of lysine methylation on histone tails is a well-established mechanism to tune gene expression, the existence of a similar arginine demethylation process is controversial. Here, the authors show that some jumonji enzymes possess both lysine and arginine demethylase activity in vitro.

    • Louise J. Walport
    • , Richard J. Hopkinson
    •  & Christopher J. Schofield
  • Article
    | Open Access

    Cardiac voltage-gated sodium channels (Nav1.5) are crucial regulators of heart electric activity. Here the authors show that palmitoylation, a process of lipid modification of cysteine residues, modulates Nav1.5 function and affects cardiomyocyte excitability, representing a potential target in treating cardiac diseases.

    • Zifan Pei
    • , Yucheng Xiao
    •  & Theodore R. Cummins
  • Article
    | Open Access

    Histone H3K4 methylation affects gene transcription from yeast to humans. Here, the authors show that Set1 and Jhd2, the only H3K4 methyltransferase and H3K4 demethylase, respectively, in budding yeast, co-regulate both positive and negative transcription mediated by nucleosomal turnover and occupancy.

    • Saravanan Ramakrishnan
    • , Srijana Pokhrel
    •  & Mahesh B. Chandrasekharan
  • Article
    | Open Access

    STING is essential for the type I interferon immune response to foreign DNA. Here, the authors show that palmitoylation of STING at the Golgi is required for activating downstream signalling, and increased Golgi localization of certain STING variants may cause autoimmune disease in some cases.

    • Kojiro Mukai
    • , Hiroyasu Konno
    •  & Tomohiko Taguchi