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https://www.readbyqxmd.com/read/28320742/development-of-lc3-gabarap-sensors-containing-a-lir-and-a-hydrophobic-domain-to-monitor-autophagy
#1
You-Kyung Lee, Yong-Woo Jun, Ha-Eun Choi, Yang Hoon Huh, Bong-Kiun Kaang, Deok-Jin Jang, Jin-A Lee
Macroautophagy allows for bulk degradation of cytosolic components in lysosomes. Overexpression of GFP/RFP-LC3/GABARAP is commonly used to monitor autophagosomes, a hallmark of autophagy, despite artifacts related to their overexpression. Here, we developed new sensors that detect endogenous LC3/GABARAP proteins at the autophagosome using an LC3-interacting region (LIR) and a short hydrophobic domain (HyD). Among HyD-LIR-GFP sensors harboring LIR motifs of 34 known LC3-binding proteins, HyD-LIR(TP)-GFP using the LIR motif from TP53INP2 allowed detection of all LC3/GABARAPs-positive autophagosomes...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28320741/hypoxia-enhances-antibody-dependent-dengue-virus-infection
#2
Esther Shuyi Gan, Wei Fun Cheong, Kuan Rong Chan, Eugenia Ziying Ong, Xiaoran Chai, Hwee Cheng Tan, Sujoy Ghosh, Markus R Wenk, Eng Eong Ooi
Dengue virus (DENV) has been found to replicate in lymphoid organs such as the lymph nodes, spleen, and liver in post-mortem analysis. These organs are known to have low oxygen levels (~0.5-4.5% O2) due to the vascular anatomy. However, how physiologically low levels of oxygen affect DENV infection via hypoxia-induced changes in the immune response remains unknown. Here, we show that monocytes adapted to 3% O2 show greater susceptibility to antibody-dependent enhancement of DENV infection. Low oxygen level induces HIF1α-dependent upregulation of fragment crystallizable gamma receptor IIA (FcγRIIA) as well as HIF1α-independent alterations in membrane ether lipid concentrations...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28320740/non-canonical-aging-model-systems-and-why-we-need-them
#3
Dario Riccardo Valenzano, Aziz Aboobaker, Andrei Seluanov, Vera Gorbunova
No abstract text is available yet for this article.
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28320739/a-covalently-bound-inhibitor-triggers-ezh2-degradation-through-chip-mediated-ubiquitination
#4
Xu Wang, Wei Cao, Jianjun Zhang, Ming Yan, Qin Xu, Xiangbing Wu, Lixin Wan, Zhiyuan Zhang, Chenping Zhang, Xing Qin, Meng Xiao, Dongxia Ye, Yuyang Liu, Zeguang Han, Shaomeng Wang, Li Mao, Wenyi Wei, Wantao Chen
Enhancer of zeste homolog 2 (EZH2) has been characterized as a critical oncogene and a promising drug target in human malignant tumors. The current EZH2 inhibitors strongly suppress the enhanced enzymatic function of mutant EZH2 in some lymphomas. However, the recent identification of a PRC2- and methyltransferase-independent role of EZH2 indicates that a complete suppression of all oncogenic functions of EZH2 is needed. Here, we report a unique EZH2-targeting strategy by identifying a gambogenic acid (GNA) derivative as a novel agent that specifically and covalently bound to Cys668 within the EZH2-SET domain, triggering EZH2 degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28320738/and-akt-ion-iqgap1-in-control-of-signaling-pathways
#5
Suyong Choi, Richard A Anderson
No abstract text is available yet for this article.
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28320737/mir-31-mutants-reveal-continuous-glial-homeostasis-in-the-adult-drosophila-brain
#6
Lynette Caizhen Foo, Shilin Song, Stephen Michael Cohen
The study of adult neural cell production has concentrated on neurogenesis. The mechanisms controlling adult gliogenesis are still poorly understood. Here, we provide evidence for a homeostatic process that maintains the population of glial cells in the Drosophila adult brain. Flies lacking microRNA miR-31a start adult life with a normal complement of glia, but transiently lose glia due to apoptosis. miR-31a expression identifies a subset of predominantly gliogenic adult neural progenitor cells. Failure to limit expression of the predicted E3 ubiquitin ligase, Rchy1, in these cells results in glial loss...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28320736/arabidopsis-retinoblastoma-related-directly-regulates-dna-damage-responses-through-functions-beyond-cell-cycle-control
#7
Beatrix M Horvath, Hana Kourova, Szilvia Nagy, Edit Nemeth, Zoltan Magyar, Csaba Papdi, Zaki Ahmad, Gabino F Sanchez-Perez, Serena Perilli, Ikram Blilou, Aladár Pettkó-Szandtner, Zsuzsanna Darula, Tamas Meszaros, Pavla Binarova, Laszlo Bogre, Ben Scheres
The rapidly proliferating cells in plant meristems must be protected from genome damage. Here, we show that the regulatory role of the Arabidopsis RETINOBLASTOMA RELATED (RBR) in cell proliferation can be separated from a novel function in safeguarding genome integrity. Upon DNA damage, RBR and its binding partner E2FA are recruited to heterochromatic γH2AX-labelled DNA damage foci in an ATM- and ATR-dependent manner. These γH2AX-labelled DNA lesions are more dispersedly occupied by the conserved repair protein, AtBRCA1, which can also co-localise with RBR foci...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28320735/the-retinoblastoma-homolog-rbr1-mediates-localization-of-the-repair-protein-rad51-to-dna-lesions-in-arabidopsis
#8
Sascha Biedermann, Hirofumi Harashima, Poyu Chen, Maren Heese, Daniel Bouyer, Kostika Sofroni, Arp Schnittger
The retinoblastoma protein (Rb), which typically functions as a transcriptional repressor of E2F-regulated genes, represents a major control hub of the cell cycle. Here, we show that loss of the Arabidopsis Rb homolog RETINOBLASTOMA-RELATED 1 (RBR1) leads to cell death, especially upon exposure to genotoxic drugs such as the environmental toxin aluminum. While cell death can be suppressed by reduced cell-proliferation rates, rbr1 mutant cells exhibit elevated levels of DNA lesions, indicating a direct role of RBR1 in the DNA-damage response (DDR)...
March 20, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28314781/sex-specific-reciprocal-regulation-of-er%C3%AE-and-mir-22-controls-muscle-lipid-metabolism-in-male-mice
#9
Judith Schweisgut, Christian Schutt, Stas Wüst, Astrid Wietelmann, Bart Ghesquière, Peter Carmeliet, Stefan Dröse, Kenneth S Korach, Thomas Braun, Thomas Boettger
Control of energy homeostasis and metabolism is achieved by integrating numerous pathways, and miRNAs are involved in this process by regulating expression of multiple target genes. However, relatively little is known about the posttranscriptional processing of miRNAs and a potential role for the precursors they derive from. Here, we demonstrate that mature miRNA-22 is more abundant in muscle from male mice relative to females and that this enables sex-specific regulation of muscular lipid metabolism and body weight by repressing estrogen receptor alpha (ERα) expression...
March 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28314780/non-coding-rnas-the-dark-side-of-nuclear-mitochondrial-communication
#10
REVIEW
Roberto Vendramin, Jean-Christophe Marine, Eleonora Leucci
Mitochondria are critical hubs for the integration of several key metabolic processes implicated in cell growth and survival. They originated from bacterial ancestors through endosymbiosis, following the transfer of more than 90% of their endosymbiont genome to the host cell nucleus. Over time, a mutually beneficial symbiotic relationship has been established, which relies on continuous and elaborate signaling mechanisms between this life-essential organelle and its host. The ability of mitochondria to signal their functional state and trigger compensatory and adaptive cellular responses has long been recognized, but the underlying molecular mechanisms involved have remained poorly understood...
March 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28314779/an-atr-dependent-function-for-the-ddx19-rna-helicase-in-nuclear-r-loop-metabolism
#11
Dana Hodroj, Bénédicte Recolin, Kamar Serhal, Susan Martinez, Nikolay Tsanov, Raghida Abou Merhi, Domenico Maiorano
Coordination between transcription and replication is crucial in the maintenance of genome integrity. Disturbance of these processes leads to accumulation of aberrant DNA:RNA hybrids (R-loops) that, if unresolved, generate DNA damage and genomic instability. Here we report a novel, unexpected role for the nucleopore-associated mRNA export factor Ddx19 in removing nuclear R-loops formed upon replication stress or DNA damage. We show, in live cells, that Ddx19 transiently relocalizes from the nucleopore to the nucleus upon DNA damage, in an ATR/Chk1-dependent manner, and that Ddx19 nuclear relocalization is required to clear R-loops...
March 17, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28302655/judging-a-tumor-cell-by-its-cover-a-matter-of-mitochondrial-contact-sites
#12
Sowmya Lakshminarayanan, Luca Scorrano
No abstract text is available yet for this article.
March 16, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28298434/everything-has-its-time-id2-clocks-embryonic-specification-of-lgr5-gut-stem-cells
#13
Kai Kretzschmar, Hans Clevers
No abstract text is available yet for this article.
March 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28298433/re-evaluating-the-foundations-of-lncrna-polycomb-function
#14
Mario R Blanco, Mitchell Guttman
No abstract text is available yet for this article.
March 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28292785/recruitment-and-positioning-determine-the-specific-role-of-the-xpf-ercc1-endonuclease-in-interstrand-crosslink-repair
#15
Daisy Klein Douwel, Wouter S Hoogenboom, Rick Acm Boonen, Puck Knipscheer
XPF-ERCC1 is a structure-specific endonuclease pivotal for several DNA repair pathways and, when mutated, can cause multiple diseases. Although the disease-specific mutations are thought to affect different DNA repair pathways, the molecular basis for this is unknown. Here we examine the function of XPF-ERCC1 in DNA interstrand crosslink (ICL) repair. We used Xenopus egg extracts to measure both ICL and nucleotide excision repair, and we identified mutations that are specifically defective in ICL repair. One of these separation-of-function mutations resides in the helicase-like domain of XPF and disrupts binding to SLX4 and recruitment to the ICL A small deletion in the same domain supports recruitment of XPF to the ICL, but inhibited the unhooking incisions most likely by disrupting a second, transient interaction with SLX4...
March 14, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28289055/written-in-bone-young-bone-makes-young-blood
#16
Karin Gustafsson, David T Scadden
No abstract text is available yet for this article.
March 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28289054/final-touches-and-quality-control-on-the-assembly-of-the-eukaryotic-ribosome
#17
Aida Razi, Joaquin Ortega
No abstract text is available yet for this article.
March 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28283582/self-organized-developmental-patterning-and-differentiation-in-cerebral-organoids
#18
Magdalena Renner, Madeline A Lancaster, Shan Bian, Heejin Choi, Taeyun Ku, Angela Peer, Kwanghun Chung, Juergen A Knoblich
Cerebral organoids recapitulate human brain development at a considerable level of detail, even in the absence of externally added signaling factors. The patterning events driving this self-organization are currently unknown. Here, we examine the developmental and differentiative capacity of cerebral organoids. Focusing on forebrain regions, we demonstrate the presence of a variety of discrete ventral and dorsal regions. Clearing and subsequent 3D reconstruction of entire organoids reveal that many of these regions are interconnected, suggesting that the entire range of dorso-ventral identities can be generated within continuous neuroepithelia...
March 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28283581/mtcl1-plays-an-essential-role-in-maintaining-purkinje-neuron-axon-initial-segment
#19
Tomoko Satake, Kazunari Yamashita, Kenji Hayashi, Satoko Miyatake, Miwa Tamura-Nakano, Hiroshi Doi, Yasuhide Furuta, Go Shioi, Eriko Miura, Yukari H Takeo, Kunihiro Yoshida, Hiroyuki Yahikozawa, Naomichi Matsumoto, Michisuke Yuzaki, Atsushi Suzuki
The axon initial segment (AIS) is a specialized domain essential for neuronal function, the formation of which begins with localization of an ankyrin-G (AnkG) scaffold. However, the mechanism directing and maintaining AnkG localization is largely unknown. In this study, we demonstrate that in vivo knockdown of microtubule cross-linking factor 1 (MTCL1) in cerebellar Purkinje cells causes loss of axonal polarity coupled with AnkG mislocalization. MTCL1 lacking MT-stabilizing activity failed to restore these defects, and stable MT bundles spanning the AIS were disorganized in knockdown cells...
March 10, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28283580/er-mitochondria-contacts-control-surface-glycan-expression-and-sensitivity-to-killer-lymphocytes-in-glioma-stem-like-cells
#20
Esen Yonca Bassoy, Atsuko Kasahara, Valentina Chiusolo, Guillaume Jacquemin, Emma Boydell, Sebastian Zamorano, Cristina Riccadonna, Serena Pellegatta, Nicolas Hulo, Valérie Dutoit, Madiha Derouazi, Pierre Yves Dietrich, Paul R Walker, Denis Martinvalet
Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem-like cells (GSC) being more sensitive to cytotoxic lymphocyte-mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER-mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER-mitochondria contacts compared to GDCs...
March 10, 2017: EMBO Journal
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