Post-translational modifications articles within Nature Communications

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  • Article
    | Open Access

    Here, Dirk Lefeber and colleagues identify functional mutations in ATP6AP1 encoding Ac45. The authors show that Ac45 is the functional ortholog of yeast V-ATPase assembly factor Voa1 and provide evidence for tissue-specific Ac45 processing, associated with the clinical phenotype of immunodeficiency, hepatopathy, and neurocognitive abnormalities.

    • Eric J. R. Jansen
    • , Sharita Timal
    •  & Dirk J. Lefeber

  • Article
    | Open Access

    NK cell activation requires multiple signals. Here the authors show that while NKG2D, 2B4, or DNAM-1 receptor activation is insufficient to induce cytokine production, these signals synergize by Vav-1-mediated NF-κB multiphosphorylation, and this signaling checkpoint is defective in X-linked lymphoproliferative disease.

    • Hyung-Joon Kwon
    • , Go-Eun Choi
    •  & Hun Sik Kim

  • Article
    | Open Access

    The spectraplakin protein ACF7 binds to actin at focal adhesions and targets microtubule plus ends to focal adhesions, promoting their disassembly. Here the authors reveal that ACF7 is phosphorylated by Src/FAK, and this regulates actin binding and focal adhesion dynamics in vitro and in vivo.

    • Jiping Yue
    • , Yao Zhang
    •  & Xiaoyang Wu

  • Article
    | Open Access

    Phytochromes regulate plant responses to environmental light conditions but despite extensive research the initial events in phytochrome signaling remain uncertain. Here, Shin et al. provide evidence that phytochrome phosphorylates target proteins via kinase activity in the N-terminal core domain.

    • Ah-Young Shin
    • , Yun-Jeong Han
    •  & Jeong-Il Kim

  • Article
    | Open Access

    F1FO ATP synthase is a critical enzyme for the maintenance of mitochondrial function. Here the authors demonstrate that loss of the F1FO-ATP synthase subunit OSCP and the interaction of OSCP with Aβ peptide in Alzheimer’s disease patients and mouse models lead to F1FO-ATP synthase deregulation and disruption of synaptic mitochondrial function.

    • Simon J. Beck
    • , Lan Guo
    •  & Heng Du

  • Article
    | Open Access

    Wnt/β-catenin signalling directs several developmental processes and is aberrantly activated in several cancers. Here the authors implicate Tankyrase—previously shown to target the scaffolding protein Axin for proteolysis—in early Wnt signalling by promoting the interaction between Axin and the Wnt co-receptor LRP6.

    • Eungi Yang
    • , Ofelia Tacchelly-Benites
    •  & Yashi Ahmed

  • Article
    | Open Access

    Cells delay completion of cytokinesis when chromatin is trapped at the intercellular bridge. Here, Petsalaki and Zachos report that Cdc-like kinases (Clks) 1, 2 and 4 localize to the midbody and phosphorylate the mitotic kinase Aurora B, imposing the abscission checkpoint to prevent premature abscission and chromatin breakage.

    • Eleni Petsalaki
    •  & George Zachos

  • Article
    | Open Access

    Kinase inhibitors are important drugs and usually target the ATP binding pocket of kinases. Here, Kii et al.report a completely new type of kinase inhibitor that specifically targets the protein folding intermediate state, but not the mature form, of the protein kinase DYRK1A.

    • Isao Kii
    • , Yuto Sumida
    •  & Masatoshi Hagiwara

  • Article
    | Open Access

    The repair of double-strand DNA breaks by homologous recombination requires resection of the DNA ends. Here the authors show that in Schizosaccharomyces pombe and human cells, Wdr70 is recruited as part of the CRL4 complex to promote ubiquitination of H2B and allow Exo1-mediated resection.

    • Ming Zeng
    • , Laifeng Ren
    •  & Cong Liu

  • Article
    | Open Access

    Mep2 proteins are tightly regulated fungal ammonium transporters. Here, the authors report the crystal structures of closed states of Mep2 proteins and propose a model for their regulation by comparing them with the open ammonium transporters of bacteria.

    • Bert van den Berg
    • , Anupama Chembath
    •  & Julian C. Rutherford

  • Article
    | Open Access

    Protein aggregation plays a crucial role in several neurodegenerative diseases. Here the authors demonstrate that phosphorylation of β-amyloid aggregates—the pathological hallmark of Alzheimer's disease—can change the molecular properties of aggregates, suggesting how phosphorylation contributes to disease progression.

    • Nasrollah Rezaei-Ghaleh
    • , Mehriar Amininasab
    •  & Markus Zweckstetter

  • Article
    | Open Access

    Although IFNγ is a Th1 signature cytokine and is repressed in Th2 cells, it is reactivated in a subset of memory Th2 cells. Here the authors show that Hdac2 is released from Gata3 by Akt-mediated phosphorylation, leading to transcriptional derepression of Tbx21 and IFNγin these cells.

    • Hiroyuki Hosokawa
    • , Tomoaki Tanaka
    •  & Toshinori Nakayama

  • Article
    | Open Access

    Ternary complex (TC) and eIF4F complex assembly are rate-limiting steps in translation initiation that are regulated by eIF2α phosphorylation and the mTOR/4E-BP pathway. Here the authors show that the protein kinases mTORC1 and CK2 coordinate TC and eIF4F complex assembly through eIF2β to stimulate cell proliferation.

    • Valentina Gandin
    • , Laia Masvidal
    •  & Ivan Topisirovic

  • Article
    | Open Access

    Temporal regulation of microtubule dynamics in mitosis can be achieved by phosphorylation of microtubule plus-end proteins. Here, the authors show that Aurora B and CDK1 phosphorylate EB2, which changes microtubule binding affinity and controls kinetochore microtubule dynamics and genome stability.

    • Makoto Iimori
    • , Sugiko Watanabe
    •  & Yoshihiko Maehara

  • Article
    | Open Access

    C/EBPα is an essential transcription factor for myeloid lineage commitment. Here, the authors show that acetylation of C/EBPα at K298 and K302, mediated at least in part by GCN5, impairs C/EBPα DNA binding ability and modulates C/EBPα transcriptional activity.

    • Deepak Bararia
    • , Hui Si Kwok
    •  & Daniel G. Tenen

  • Article
    | Open Access

    MiR-34 is a tumour suppressor microRNA known to be upregulated by p53 after DNA damage and plays a critical role in cell cycle arrest and apoptosis. Here the authors show the cell maintains an inactive pool of miR-34 which is rapidly activated after damage via ATM-dependent phosphorylation.

    • David W. Salzman
    • , Kotoka Nakamura
    •  & Joanne B. Weidhaas

  • Article
    | Open Access

    Organic cation transporters are important drug transporters that influence therapeutic outcomes. Here, the authors find that these transporters are regulated by tyrosine phosphorylation and propose that tyrosine kinase inhibitors can influence drug transporter function through post-translational mechanisms.

    • Jason A. Sprowl
    • , Su Sien Ong
    •  & Navjotsingh Pabla

  • Article
    | Open Access

    The Anaphase Promoting Complex/Cyclosome (APC/C) and its co-activator Cdc20 regulate mitotic progression, but both are also present in interphase. Here Hein and Nilsson show that Cyclin A2–CDK2 phosphorylates Cdc20 to inhibit APC/C–Cdc20 activity during this cell cycle phase to promote mitotic entry.

    • Jamin B. Hein
    •  & Jakob Nilsson

  • Article
    | Open Access

    SIRT7 is a protein deacetylase with important roles in rRNA synthesis, ribosome biogenesis and cell proliferation. Here the authors show a role of SIRT7 in rRNA maturation via deacetylation of U3-55k, a core component of the U3 snoRNP complex.

    • Sifan Chen
    • , Maximilian Felix Blank
    •  & Renate Voit

  • Article
    | Open Access

    Rab7 is a critical GTPase for endosome maturation and it is implicated in the endocytic traffic of several receptors, including EGFR. In this study, the authors reveal the potential role of PTEN in the endocytic trafficking pathway of EGFR, which is dependent on its phosphatase activity through the direct post-translational modification of Rab7.

    • Swapnil Rohidas Shinde
    •  & Subbareddy Maddika

  • Article
    | Open Access

    UPF1 is a central Nonsense-mediated mRNA decay—(NMD), a mechanism to degrade mRNAs containing premature translation termination codons-factor—whose phosphorylation is key to triggering NMD. Here the authors show that the DHX34 helicase acts as a scaffold in promoting UPF1 phosphorylation by SMG1 to promotes NMD.

    • Roberto Melero
    • , Nele Hug
    •  & Oscar Llorca

  • Article
    | Open Access

    Ribosome biogenesis involves the hierarchical assembly of several proteins and RNA components. Here the authors describe a mechanism for ribosomal protein S3 incorporation into 40S ribosomal subunits that involves S3 dimerization and stepwise incorporation of two distinct S3 interaction domains coupled to release of ribosomal maturation factors.

    • Valentin Mitterer
    • , Guillaume Murat
    •  & Brigitte Pertschy

  • Article
    | Open Access

    While ERK signalling can produce switch-like cell behaviour, phosphorylation of ERK increases linearly with extracellular signals. Here, the authors solve this seeming contradiction by showing that nuclear translocation of ERK behaves in a switch-like manner and is controlled by ERK activity.

    • Yuki Shindo
    • , Kazunari Iwamoto
    •  & Koichi Takahashi

  • Article
    | Open Access

    The spatial location of proteins within a cell is a key element of protein function. Here the authors describe hyperLOPIT—a proteomics workflow that allows the simultaneous assignment of thousands of proteins to subcellular niches with high resolution—and apply it to mouse pluripotent stem cells.

    • Andy Christoforou
    • , Claire M. Mulvey
    •  & Kathryn S. Lilley

  • Article
    | Open Access

    Alzheimer's disease is linked to metabolic syndrome and Type-2 diabetes, but the mechanism behind this association is unclear. Here, the authors show that elevated glucose and amyloid ß work together to increase nitrosative stress, leading to aberrant mitochondrial activity and synaptic dysfunction.

    • Mohd Waseem Akhtar
    • , Sara Sanz-Blasco
    •  & Stuart A. Lipton

  • Article
    | Open Access

    The tumor suppressor BAP1 is activated by ASXL1 to deubiquitinate mono-ubiquitinated H2A at K119 in Polycomb gene repression. Here, the authors show how BAP1’s C-terminal extension auto-recruits it to nucleosomes, where the DEUBAD domain of ASXL1 increases BAP1’s affinity for ubiquitin to drive deubiquitination.

    • Danny D. Sahtoe
    • , Willem J. van Dijk
    •  & Titia K. Sixma

  • Article
    | Open Access

    DCAF1 (VprBP), an HIV target protein, is a component of an ubiquitin ligase complex involved in developmental processes in plants and animals. Here, DCAF1 is shown to be vital for activation-induced T cell growth and proliferation, partly by being required for p53’s ubiquitination and degradation.

    • Zengli Guo
    • , Qing Kong
    •  & Yisong Y. Wan

  • Article
    | Open Access

    Several histone modifiers have been implicated in the survival of multiple myeloma cells. Here, the authors reveal a role for the histone demethylase KDM3A in the survival of this haematologic cancer, and show that mechanistically KDM3A removes H3K9 methylation from the promoters of KLF2 and IRF4, genes essential for myeloma cell survival.

    • Hiroto Ohguchi
    • , Teru Hideshima
    •  & Kenneth C. Anderson

  • Article
    | Open Access

    Different fibroblast growth factor (fgf) ligands elicit specific biological responses, but the mechanism directing this specificity is unknown. Here the authors show that fgf1 and fgf2 impose specific reorganizations on the fgf receptor dimer trans-membrane helices that result in distinct level of receptor activation.

    • Sarvenaz Sarabipour
    •  & Kalina Hristova

  • Article
    | Open Access

    The linker histone H1 is highly abundant and regulates DNA accessibility by compacting chromatin. Here the authors analyze transcription factor binding to nucleosomes and show that histone H1 suppresses unwrapping but does not directly block the binding of transcription factors.

    • Morgan Bernier
    • , Yi Luo
    •  & Michael G. Poirier

  • Article
    | Open Access

    Separase-mediated cleavage of pericentrin is an essential step for centriole separation during mitotic exit. Here, Kim et al.show that pericentrin has to be phosphorylated by PLK1 in order to be cleaved by separase, which provides an additional layer of regulation for centriole separation during mitotic exit.

    • Jaeyoun Kim
    • , Kwanwoo Lee
    •  & Kunsoo Rhee

  • Article
    | Open Access

    Changes in environment are known to alter reward system responses, although the underlying mechanisms are unclear. Here, Engmann et al.show that DARPP-32 interacts directly with β-adducin in the mouse striatum to regulate structural and behavioural plasticity in response to novel environment and drug exposure.

    • Olivia Engmann
    • , Albert Giralt
    •  & Jean-Antoine Girault

  • Article
    | Open Access

    Centriolar satellites (CS) dynamically remodel in response to cellular stress. Here the authors describe a mechanism for stress-mediated remodelling, whereby CEP131 is phosphorylated downstream of p38, creating binding sites for 14-3-3 that lead to the sequestration of CEP131 in the cytoplasm and disassembly of CS.

    • Maxim A. X. Tollenaere
    • , Bine H. Villumsen
    •  & Simon Bekker-Jensen

  • Article
    | Open Access

    AMPK senses cellular energy and switches off pathways involved in protein and fatty acid synthesis, but the selectivity of AMPK for different pathways is unclear. Here, the authors show that PIAS4-dependent SUMOylation and inactivation of AMPK preferentially restores activity of the mTORC1 pathway.

    • Yan Yan
    • , Saara Ollila
    •  & Tomi P. Mäkelä

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