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https://www.readbyqxmd.com/read/28330855/conserved-atg8-recognition-sites-mediate-atg4-association-with-autophagosomal-membranes-and-atg8-deconjugation
#1
Susana Abreu, Franziska Kriegenburg, Rubén Gómez-Sánchez, Muriel Mari, Jana Sánchez-Wandelmer, Mads Skytte Rasmussen, Rodrigo Soares Guimarães, Bettina Zens, Martina Schuschnig, Ralph Hardenberg, Matthias Peter, Terje Johansen, Claudine Kraft, Sascha Martens, Fulvio Reggiori
Deconjugation of the Atg8/LC3 protein family members from phosphatidylethanolamine (PE) by Atg4 proteases is essential for autophagy progression, but how this event is regulated remains to be understood. Here, we show that yeast Atg4 is recruited onto autophagosomal membranes by direct binding to Atg8 via two evolutionarily conserved Atg8 recognition sites, a classical LC3-interacting region (LIR) at the C-terminus of the protein and a novel motif at the N-terminus. Although both sites are important for Atg4-Atg8 interaction in vivo, only the new N-terminal motif, close to the catalytic center, plays a key role in Atg4 recruitment to autophagosomal membranes and specific Atg8 deconjugation...
March 22, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28325773/cue-domain-containing-protein-2-promotes-the-warburg-effect-and-tumorigenesis
#2
Xiuying Zhong, Shengya Tian, Xiang Zhang, Xinwei Diao, Fangting Dong, Jie Yang, Zhaoyong Li, Linchong Sun, Lin Wang, Xiaoping He, Gongwei Wu, Xin Hu, Lihua Wang, Libing Song, Huafeng Zhang, Xin Pan, Ailing Li, Ping Gao
Cancer progression depends on cellular metabolic reprogramming as both direct and indirect consequence of oncogenic lesions; however, the underlying mechanisms are still poorly understood. Here, we report that CUEDC2 (CUE domain-containing protein 2) plays a vital role in facilitating aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we show that CUEDC2 upregulates the two key glycolytic proteins GLUT3 and LDHA via interacting with the glucocorticoid receptor (GR) or 14-3-3ζ, respectively...
March 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28325772/tet3-mediated-dna-oxidation-promotes-atr-dependent-dna-damage-response
#3
Dewei Jiang, Shu Wei, Fei Chen, Ying Zhang, Jiali Li
An efficient, accurate, and timely DNA damage response (DDR) is crucial for the maintenance of genome integrity. Here, we report that ten-eleven translocation dioxygenase (TET) 3-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in response to ATR-dependent DDR regulates DNA repair. ATR-dependent DDR leads to dynamic changes in 5hmC levels and TET3 enzymatic activity. We show that TET3 is an ATR kinase target that oxidizes DNA during ATR-dependent DNA damage repair. Modulation of TET3 expression and activity affects DNA damage signaling and DNA repair and consequently cell death...
March 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28283533/improving-research-misconduct-policies-evidence-from-social-psychology-could-inform-better-policies-to-prevent-misconduct-in-research
#4
Barbara K Redman, Arthur L Caplan
No abstract text is available yet for this article.
March 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28283532/molecular-architecture-of-the-n-type-atpase-rotor-ring-from-burkholderia-pseudomallei
#5
Sarah Schulz, Martin Wilkes, Deryck J Mills, Werner Kühlbrandt, Thomas Meier
The genome of the highly infectious bacterium Burkholderia pseudomallei harbors an atp operon that encodes an N-type rotary ATPase, in addition to an operon for a regular F-type rotary ATPase. The molecular architecture of N-type ATPases is unknown and their biochemical properties and cellular functions are largely unexplored. We studied the B. pseudomallei N1No-type ATPase and investigated the structure and ion specificity of its membrane-embedded c-ring rotor by single-particle electron cryo-microscopy. Of several amphiphilic compounds tested for solubilizing the complex, the choice of the low-density, low-CMC detergent LDAO was optimal in terms of map quality and resolution...
March 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28283531/restoring-tropical-rain-forests-policies-to-protect-tropical-rain-forests-and-efficient-restoration-measures-require-research-based-evidence-on-biodiversity-and-ecology
#6
https://www.readbyqxmd.com/read/28274952/charities-and-the-lure-of-capitalism-philanthropies-dedicated-to-finding-cures-for-rare-diseases-explore-new-models-for-funding-and-cooperation-to-accelerate-research-and-drug-development
#7
https://www.readbyqxmd.com/read/28274951/tgf%C3%AE-1-induced-leucine-limitation-uncovered-by-differential-ribosome-codon-reading
#8
Fabricio Loayza-Puch, Koos Rooijers, Jelle Zijlstra, Behzad Moumbeini, Esther A Zaal, Joachim F Oude Vrielink, Rui Lopes, Alejandro Pineiro Ugalde, Celia R Berkers, Reuven Agami
Cancer cells modulate their metabolic networks to support cell proliferation and a higher demand of building blocks. These changes may restrict the availability of certain amino acids for protein synthesis, which can be utilized for cancer therapy. However, little is known about the amino acid demand changes occurring during aggressive and invasive stages of cancer. Recently, we developed diricore, an approach based on ribosome profiling that can uncover amino acid limitations. Here, we applied diricore to a cellular model in which epithelial breast cells respond rapidly to TGFβ1, a cytokine essential for cancer progression and metastasis, and uncovered shortage of leucine...
March 8, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28270525/adipocyte-sirt1-controls-systemic-insulin-sensitivity-by-modulating-macrophages-in-adipose-tissue
#9
Xiaoyan Hui, Mingliang Zhang, Ping Gu, Kuai Li, Yuan Gao, Donghai Wu, Yu Wang, Aimin Xu
Adipose tissue inflammation, characterized by augmented infiltration and altered polarization of macrophages, contributes to insulin resistance and its associated metabolic diseases. The NAD(+)-dependent deacetylase SIRT1 serves as a guardian against metabolic disorders in multiple tissues. To dissect the roles of SIRT1 in adipose tissues, metabolic phenotypes of mice with selective ablation of SIRT1 in adipocytes and myeloid cells were monitored. Compared to myeloid-specific SIRT1 depletion, mice with adipocyte-selective deletion of SIRT1 are more susceptible to diet-induced insulin resistance...
March 7, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28264987/nuclear-retention-of-the-lncrna-snhg1-by-doxorubicin-attenuates-hnrnpc-p53-protein-interactions
#10
Yuan Shen, Shanshan Liu, Jiao Fan, Yinghua Jin, Baolei Tian, Xiaofei Zheng, Hanjiang Fu
The protein p53 plays a crucial role in the regulation of cellular responses to diverse stresses. Thus, a major priority in cell biology is to define the mechanisms that regulate p53 activity in response to stresses or maintain it at basal levels under normal conditions. Moreover, further investigation is required to establish whether RNA participates in regulating p53's interaction with other proteins. Here, by conducting systematic experiments, we discovered a p53 interactor-hnRNPC-that directly binds to p53, destabilizes it, and prevents its activation under normal conditions...
March 6, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28242749/how-we-become-ill-investigating-emergent-properties-of-biological-systems-could-help-to-better-understand-the-pathology-of-diseases
#11
Patrick Finzer
No abstract text is available yet for this article.
February 27, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28242748/cep78-controls-centrosome-homeostasis-by-inhibiting-edd-dyrk2-ddb1-vpr-bp
#12
Delowar Hossain, Yalda Javadi Esfehani, Arindam Das, William Y Tsang
The centrosome plays a critical role in various cellular processes including cell division and cilia formation, and deregulation of centrosome homeostasis is a hallmark feature of many human diseases. Here, we show that centrosomal protein of 78 kDa (Cep78) localizes to mature centrioles and directly interacts with viral protein R binding protein (VprBP). Although VprBP is a component of two distinct E3 ubiquitin ligases, EDD-DYRK2-DDB1(Vpr)(BP) and CRL4(Vpr)(BP), Cep78 binds specifically to EDD-DYRK2-DDB1(Vpr)(BP) and inhibits its activity...
February 27, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28232627/microrna-independent-functions-of-dgcr8-are-essential-for-neocortical-development-and-tbr1-expression
#13
Federica Marinaro, Matteo J Marzi, Nadin Hoffmann, Hayder Amin, Roberta Pelizzoli, Francesco Niola, Francesco Nicassio, Davide De Pietri Tonelli
Recent evidence indicates that the miRNA biogenesis factors DROSHA, DGCR8, and DICER exert non-overlapping functions, and have also roles in miRNA-independent regulatory mechanisms. However, it is currently unknown whether miRNA-independent functions of DGCR8 play any role in the maintenance of neuronal progenitors and during corticogenesis. Here, by phenotypic comparison of cortices from conditional Dgcr8 and Dicer knockout mice, we show that Dgcr8 deletion, in contrast to Dicer depletion, leads to premature differentiation of neural progenitor cells and overproduction of TBR1-positive neurons...
February 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28223321/a-non-canonical-function-of-ezh2-preserves-immune-homeostasis
#14
Ajithkumar Vasanthakumar, Dakang Xu, Aaron Tl Lun, Andrew J Kueh, Klaas Pjm van Gisbergen, Nadia Iannarella, Xiaofang Li, Liang Yu, Die Wang, Bryan Rg Williams, Stanley Cw Lee, Ian J Majewski, Dale I Godfrey, Gordon K Smyth, Warren S Alexander, Marco J Herold, Axel Kallies, Stephen L Nutt, Rhys S Allan
Enhancer of zeste 2 (Ezh2) mainly methylates lysine 27 of histone-H3 (H3K27me3) as part of the polycomb repressive complex 2 (PRC2) together with Suz12 and Eed. However, Ezh2 can also modify non-histone substrates, although it is unclear whether this mechanism has a role during development. Here, we present evidence for a chromatin-independent role of Ezh2 during T-cell development and immune homeostasis. T-cell-specific depletion of Ezh2 induces a pronounced expansion of natural killer T (NKT) cells, although Ezh2-deficient T cells maintain normal levels of H3K27me3...
February 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28219903/myc-driven-inhibition-of-the-glutamate-cysteine-ligase-promotes-glutathione-depletion-in-liver-cancer
#15
Brittany Anderton, Roman Camarda, Sanjeev Balakrishnan, Asha Balakrishnan, Rebecca A Kohnz, Lionel Lim, Kimberley J Evason, Olga Momcilovic, Klaus Kruttwig, Qiang Huang, Guowang Xu, Daniel K Nomura, Andrei Goga
How MYC reprograms metabolism in primary tumors remains poorly understood. Using integrated gene expression and metabolite profiling, we identify six pathways that are coordinately deregulated in primary MYC-driven liver tumors: glutathione metabolism; glycine, serine, and threonine metabolism; aminoacyl-tRNA biosynthesis; cysteine and methionine metabolism; ABC transporters; and mineral absorption. We then focus our attention on glutathione (GSH) and glutathione disulfide (GSSG), as they are markedly decreased in MYC-driven tumors...
February 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28219902/ndr1-protein-kinase-promotes-il-17-and-tnf-%C3%AE-mediated-inflammation-by-competitively-binding-traf3
#16
Chunmei Ma, Wenlong Lin, Zhiyong Liu, Wei Tang, Rahul Gautam, Hui Li, Youcun Qian, He Huang, Xiaojian Wang
Interleukin 17 (IL-17) is an important inducer of tissue inflammation and is involved in numerous autoimmune diseases. However, how its signal transduction is regulated is not well understood. Here, we report that nuclear Dbf2-related kinase 1 (NDR1) functions as a positive regulator of IL-17 signal transduction and IL-17-induced inflammation. NDR1 deficiency or knockdown inhibits the IL-17-induced phosphorylation of p38, ERK1/2, and p65 and the expression of chemokines and cytokines, whereas the overexpression of NDR1 promotes IL-17-induced signaling independent of its kinase activity...
February 20, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28188145/structural-studies-of-rfc-c-tf18-reveal-a-novel-chromatin-recruitment-role-for-dcc1
#17
Benjamin O Wade, Hon Wing Liu, Catarina P Samora, Frank Uhlmann, Martin R Singleton
Replication factor C complexes load and unload processivity clamps from DNA and are involved in multiple DNA replication and repair pathways. The RFC(C)(tf18) variant complex is required for activation of the intra-S-phase checkpoint at stalled replication forks and aids the establishment of sister chromatid cohesion. Unlike other RFC complexes, RFC(C)(tf18) contains two non-Rfc subunits, Dcc1 and Ctf8. Here, we present the crystal structure of the Dcc1-Ctf8 heterodimer bound to the C-terminus of Ctf18. We find that the C-terminus of Dcc1 contains three-winged helix domains, which bind to both ssDNA and dsDNA We further show that these domains are required for full recruitment of the complex to chromatin, and correct activation of the replication checkpoint...
February 10, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28219904/activity-dependent-transposition
#18
Andrew G Newman, Paraskevi Bessa, Victor Tarabykin, Prim B Singh
No abstract text is available yet for this article.
March 2017: EMBO Reports
https://www.readbyqxmd.com/read/28219901/the-role-of-scientific-self-regulation-for-the-control-of-genome-editing-in-the-human-germline-the-lessons-from-the-asilomar-and-the-napa-meetings-show-how-self-regulation-and-public-deliberation-can-lead-to-regulation-of-new-biotechnologies
#19
https://www.readbyqxmd.com/read/28202491/organoid-technologies-meet-genome-engineering
#20
REVIEW
Jing Nie, Eri Hashino
Three-dimensional (3D) stem cell differentiation cultures recently emerged as a novel model system for investigating human embryonic development and disease progression in vitro, complementing existing animal and two-dimensional (2D) cell culture models. Organoids, the 3D self-organizing structures derived from pluripotent or somatic stem cells, can recapitulate many aspects of structural organization and functionality of their in vivo organ counterparts, thus holding great promise for biomedical research and translational applications...
March 2017: EMBO Reports
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