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EMBO Reports

Ella Fung, Carmen Richter, Hong-Bin Yang, Isabell Schäffer, Roman Fischer, Benedikt M Kessler, Florian Bassermann, Vincenzo D'Angiolella
Aberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule nucleation. However, regulatory means of CEP192 have remained unknown. Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192...
January 18, 2018: EMBO Reports
Verónica Sobrino, Patricia González-Rodríguez, Valentina Annese, José López-Barneo, Ricardo Pardal
Unlike other neural peripheral organs, the adult carotid body (CB) has a remarkable structural plasticity, as it grows during acclimatization to hypoxia. The CB contains neural stem cells that can differentiate into oxygen-sensitive glomus cells. However, an extended view is that, unlike other catecholaminergic cells of the same lineage (sympathetic neurons or chromaffin cells), glomus cells can divide and thus contribute to CB hypertrophy. Here, we show that O2-sensitive mature glomus cells are post-mitotic...
January 15, 2018: EMBO Reports
Junmei Cairns, Brooke L Fridley, Gregory D Jenkins, Yongxian Zhuang, Jia Yu, Liewei Wang
AKT signaling is modulated by a complex network of regulatory proteins and is commonly deregulated in cancer. Here, we present a dual mechanism of AKT regulation by the ERBB receptor feedback inhibitor 1 (ERRFI1). We show that in cells expressing high levels of EGFR, ERRF1 inhibits growth and enhances responses to chemotherapy. This is mediated in part through the negative regulation of AKT signaling by direct ERRFI1-dependent inhibition of EGFR In cells expressing low levels of EGFR, ERRFI1 positively modulates AKT signaling by interfering with the interaction of the inactivating phosphatase PHLPP with AKT, thereby promoting cell growth and chemotherapy desensitization...
January 15, 2018: EMBO Reports
Prisca Brauns-Schubert, Florian Schubert, Manuela Wissler, Martina Weiss, Lisa Schlicher, Simon Bessler, Mariam Safavi, Cornelius Miething, Christoph Borner, Tilman Brummer, Ulrich Maurer
The acetyltransferase TIP60 is regulated by phosphorylation, and we have previously shown that phosphorylation of TIP60 on S86 by GSK-3 promotes p53-mediated induction of the BCL-2 protein PUMA. TIP60 phosphorylation by GSK-3 requires a priming phosphorylation on S90, and here, we identify CDK9 as a TIP60S90 kinase. We demonstrate that a phosphorylation-deficient mutant, TIP60S90A, exhibits reduced interaction with chromatin, histone 3 and RNA Pol II, while its association with the TIP60 complex subunit EPC1 is not affected...
January 15, 2018: EMBO Reports
Isma Bennabi, Isabelle Quéguiner, Agnieszka Kolano, Thomas Boudier, Philippe Mailly, Marie-Hélène Verlhac, Marie-Emilie Terret
Mitotic spindles assemble from two centrosomes, which are major microtubule-organizing centers (MTOCs) that contain centrioles. Meiotic spindles in oocytes, however, lack centrioles. In mouse oocytes, spindle microtubules are nucleated from multiple acentriolar MTOCs that are sorted and clustered prior to completion of spindle assembly in an "inside-out" mechanism, ending with establishment of the poles. We used HSET (kinesin-14) as a tool to shift meiotic spindle assembly toward a mitotic "outside-in" mode and analyzed the consequences on the fidelity of the division...
January 12, 2018: EMBO Reports
Yoko Otsubo, Tomohiko Matsuo, Akiko Nishimura, Masayuki Yamamoto, Akira Yamashita
Target of rapamycin (TOR) kinase controls cell growth and metabolism in response to nutrient availability. In the fission yeast Schizosaccharomyces pombe, TOR complex 1 (TORC1) promotes vegetative growth and inhibits sexual differentiation in the presence of ample nutrients. Here, we report the isolation and characterization of mutants with similar phenotypes as TORC1 mutants, in that they initiate sexual differentiation even in nutrient-rich conditions. In most mutants identified, TORC1 activity is downregulated and the mutated genes are involved in tRNA expression or modification...
January 12, 2018: EMBO Reports
Ilja Nevzorov, Ekaterina Sidorenko, Weihuan Wang, Hongxia Zhao, Maria K Vartiainen
Accurate control of macromolecule transport between nucleus and cytoplasm underlines several essential biological processes, including gene expression. According to the canonical model, nuclear import of soluble proteins is based on nuclear localization signals and transport factors. We challenge this view by showing that nuclear localization of the actin-dependent motor protein Myosin-1C (Myo1C) resembles the diffusion-retention mechanism utilized by inner nuclear membrane proteins. We show that Myo1C constantly shuttles in and out of the nucleus and that its nuclear localization does not require soluble factors, but is dependent on phosphoinositide binding...
January 12, 2018: EMBO Reports
José Luis Luján, Oliver Todt
No abstract text is available yet for this article.
January 5, 2018: EMBO Reports
Matteo Villa, Diego Bonetti, Massimo Carraro, Maria Pia Longhese
Nucleolytic processing by nucleases can be a relevant mechanism to allow repair/restart of stalled replication forks. However, nuclease action needs to be controlled to prevent overprocessing of damaged replication forks that can be detrimental to genome stability. The checkpoint protein Rad9/53BP1 is known to limit nucleolytic degradation (resection) of DNA double-strand breaks (DSBs) in both yeast and mammals. Here, we show that loss of the inhibition that Rad9 exerts on resection exacerbates the sensitivity to replication stress of Mec1/ATR-defective yeast cells by exposing stalled replication forks to Dna2-dependent degradation...
January 4, 2018: EMBO Reports
Kailiang Zhao, Yang Yang, Guang Zhang, Chenfeng Wang, Decai Wang, Mian Wu, Yide Mei
The tumor suppressor p53 plays a prominent role in the protection against cancer. The activity of p53 is mainly controlled by the ubiquitin E3 ligase Mdm2, which targets p53 for proteasomal degradation. However, the regulation of Mdm2 remains not well understood. Here, we show that MARCH7, a RING domain-containing ubiquitin E3 ligase, physically interacts with Mdm2 and is essential for maintaining the stability of Mdm2. MARCH7 catalyzes Lys63-linked polyubiquitination of Mdm2, which impedes Mdm2 autoubiquitination and degradation, thereby leading to the stabilization of Mdm2...
January 2, 2018: EMBO Reports
Carsten Janke
No abstract text is available yet for this article.
December 27, 2017: EMBO Reports
Matthias Braun, Peter Dabrock
No abstract text is available yet for this article.
December 27, 2017: EMBO Reports
Félix A Rey, Karin Stiasny, Marie-Christine Vaney, Mariano Dellarole, Franz X Heinz
Zika and dengue viruses belong to the Flavivirus genus, a close group of antigenically related viruses that cause significant arthropod-transmitted diseases throughout the globe. Although infection by a given flavivirus is thought to confer lifelong protection, some of the patient's antibodies cross-react with other flaviviruses without cross-neutralizing. The original antigenic sin phenomenon may amplify such antibodies upon subsequent heterologous flavivirus infection, potentially aggravating disease by antibody-dependent enhancement (ADE)...
December 27, 2017: EMBO Reports
David Shaw
No abstract text is available yet for this article.
December 21, 2017: EMBO Reports
Amandine Verlande, Michaela Krafčíková, David Potěšil, Lukáš Trantírek, Zbyněk Zdráhal, Moustafa Elkalaf, Jan Trnka, Karel Souček, Nora Rauch, Jens Rauch, Walter Kolch, Stjepan Uldrijan
Altered cell metabolism is a hallmark of cancer, and targeting specific metabolic nodes is considered an attractive strategy for cancer therapy. In this study, we evaluate the effects of metabolic stressors on the deregulated ERK pathway in melanoma cells bearing activating mutations of the NRAS or BRAF oncogenes. We report that metabolic stressors promote the dimerization of KSR proteins with CRAF in NRAS-mutant cells, and with oncogenic BRAF in BRAFV600E-mutant cells, thereby enhancing ERK pathway activation...
December 20, 2017: EMBO Reports
Yeon-Joo Kim, Daniel Ps Osborn, Ji-Young Lee, Masatake Araki, Kimi Araki, Timothy Mohun, Johanna Känsäkoski, Nina Brandstack, Hyun-Taek Kim, Francesc Miralles, Cheol-Hee Kim, Nigel A Brown, Hyung-Goo Kim, Juan Pedro Martinez-Barbera, Paris Ataliotis, Taneli Raivio, Lawrence C Layman, Soo-Hyun Kim
WDR11 has been implicated in congenital hypogonadotropic hypogonadism (CHH) and Kallmann syndrome (KS), human developmental genetic disorders defined by delayed puberty and infertility. However, WDR11's role in development is poorly understood. Here, we report that WDR11 modulates the Hedgehog (Hh) signalling pathway and is essential for ciliogenesis. Disruption of WDR11 expression in mouse and zebrafish results in phenotypic characteristics associated with defective Hh signalling, accompanied by dysgenesis of ciliated tissues...
December 20, 2017: EMBO Reports
Anna Antoniou, Sharof Khudayberdiev, Agata Idziak, Silvia Bicker, Ralf Jacob, Gerhard Schratt
MicroRNAs are important regulators of local protein synthesis during neuronal development. We investigated the dynamic regulation of microRNA production and found that the majority of the microRNA-generating complex, consisting of Dicer, TRBP, and PACT, specifically associates with intracellular membranes in developing neurons. Stimulation with brain-derived neurotrophic factor (BDNF), which promotes dendritogenesis, caused the redistribution of TRBP from the endoplasmic reticulum into the cytoplasm, and its dissociation from Dicer, in a Ca2+-dependent manner...
December 20, 2017: EMBO Reports
Pieterjan Dierickx, Linda W Van Laake, Niels Geijsen
The circadian clock is an evolutionarily conserved timekeeper that adapts body physiology to diurnal cycles of around 24 h by influencing a wide variety of processes such as sleep-to-wake transitions, feeding and fasting patterns, body temperature, and hormone regulation. The molecular clock machinery comprises a pathway that is driven by rhythmic docking of the transcription factors BMAL1 and CLOCK on clock-controlled output genes, which results in tissue-specific oscillatory gene expression programs. Genetic as well as environmental perturbation of the circadian clock has been implicated in various diseases ranging from sleep to metabolic disorders and cancer development...
December 19, 2017: EMBO Reports
Joana Borlido, Maximiliano A D'Angelo
No abstract text is available yet for this article.
December 18, 2017: EMBO Reports
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