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EMBO Reports

Myriam Bourens, Antoni Barrientos
Defects in mitochondrial respiratory chain complex IV (CIV) frequently cause encephalocardiomyopathies. Human CIV assembly involves 14 subunits of dual genetic origin and multiple nucleus-encoded ancillary factors. Biogenesis of the mitochondrion-encoded copper/heme-containing COX1 subunit initiates the CIV assembly process. Here, we show that the intermembrane space twin CX9C protein CMC1 forms an early CIV assembly intermediate with COX1 and two assembly factors, the cardiomyopathy proteins COA3 and COX14...
January 12, 2017: EMBO Reports
Alan Fauconnier
No abstract text is available yet for this article.
January 12, 2017: EMBO Reports
Yosua Adi Kristariyanto, Syed Arif Abdul Rehman, Simone Weidlich, Axel Knebel, Yogesh Kulathu
The eight different types of ubiquitin (Ub) chains that can be formed play important roles in diverse cellular processes. Linkage-selective recognition of Ub chains by Ub-binding domain (UBD)-containing proteins is central to coupling different Ub signals to specific cellular responses. The motif interacting with ubiquitin (MIU) is a small UBD that has been characterized for its binding to monoUb. The recently discovered deubiquitinase MINDY-1/FAM63A contains a tandem MIU repeat (tMIU) that is highly selective at binding to K48-linked polyUb...
January 12, 2017: EMBO Reports
Shin-Ichiro Hiraga, Tony Ly, Javier Garzón, Zuzana Hořejší, Yoshi-Nobu Ohkubo, Akinori Endo, Chikashi Obuse, Simon J Boulton, Angus I Lamond, Anne D Donaldson
The human RIF1 protein controls DNA replication, but the molecular mechanism is largely unknown. Here, we demonstrate that human RIF1 negatively regulates DNA replication by forming a complex with protein phosphatase 1 (PP1) that limits phosphorylation-mediated activation of the MCM replicative helicase. We identify specific residues on four MCM helicase subunits that show hyperphosphorylation upon RIF1 depletion, with the regulatory N-terminal domain of MCM4 being particularly strongly affected. In addition to this role in limiting origin activation, we discover an unexpected new role for human RIF1-PP1 in mediating efficient origin licensing...
January 11, 2017: EMBO Reports
Ye Yang, Cheng Zhou, Ying Wang, Weixiao Liu, Chao Liu, Liying Wang, Yujiao Liu, Yongliang Shang, Mingrui Li, Shuai Zhou, Yuanting Wang, Wentao Zeng, Jianli Zhou, Ran Huo, Wei Li
The functional role of the ubiquitin-proteasome pathway during maternal-to-zygotic transition (MZT) remains to be elucidated. Here we show that the E3 ubiquitin ligase, Rnf114, is highly expressed in mouse oocytes and that knockdown of Rnf114 inhibits development beyond the two-cell stage. To study the underlying mechanism, we identify its candidate substrates using a 9,000-protein microarray and validate them using an in vitro ubiquitination system. We show that five substrates could be degraded by RNF114-mediated ubiquitination, including TAB1...
January 10, 2017: EMBO Reports
Akira Mine, Tatsuya Nobori, Maria C Salazar-Rondon, Thomas M Winkelmüller, Shajahan Anver, Dieter Becker, Kenichi Tsuda
Immune signaling networks must be tunable to alleviate fitness costs associated with immunity and, at the same time, robust against pathogen interferences. How these properties mechanistically emerge in plant immune signaling networks is poorly understood. Here, we discovered a molecular mechanism by which the model plant species Arabidopsis thaliana achieves robust and tunable immunity triggered by the microbe-associated molecular pattern, flg22. Salicylic acid (SA) is a major plant immune signal molecule...
January 9, 2017: EMBO Reports
Manas Ranjan Sahoo, Swati Gaikwad, Deepak Khuperkar, Maitreyi Ashok, Mary Helen, Santosh Kumar Yadav, Aditi Singh, Indrasen Magre, Prachi Deshmukh, Supriya Dhanvijay, Pabitra Kumar Sahoo, Yogendra Ramtirtha, Mallur Srivatsan Madhusudhan, Pananghat Gayathri, Vasudevan Seshadri, Jomon Joseph
MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing. However, how miRISC identifies the target mRNA in vivo is not well understood. Here, we show that the nucleoporin Nup358 plays an important role in this process. Nup358 localizes to the nuclear pore complex and to the cytoplasmic annulate lamellae (AL), and these structures dynamically associate with two mRNP granules: processing bodies (P bodies) and stress granules (SGs)...
December 30, 2016: EMBO Reports
Francisco Sarmento Mesquita, Cláudia Brito, Maria J Mazon Moya, Jorge Campos Pinheiro, Serge Mostowy, Didier Cabanes, Sandra Sousa
During infection, plasma membrane (PM) blebs protect host cells against bacterial pore-forming toxins (PFTs), but were also proposed to promote pathogen dissemination. However, the details and impact of blebbing regulation during infection remained unclear. Here, we identify the endoplasmic reticulum chaperone Gp96 as a novel regulator of PFT-induced blebbing. Gp96 interacts with non-muscle myosin heavy chain IIA (NMHCIIA) and controls its activity and remodelling, which is required for appropriate coordination of bleb formation and retraction...
December 30, 2016: EMBO Reports
Victoria Vaccaro, Michael J Devine, Nathalie F Higgs, Josef T Kittler
Mitochondrial trafficking is influenced by neuronal activity, but it remains unclear how mitochondrial positioning influences neuronal transmission and plasticity. Here, we use live cell imaging with the genetically encoded presynaptically targeted Ca(2+) indicator, SyGCaMP5, to address whether presynaptic Ca(2+) responses are altered by mitochondria in synaptic terminals. We find that presynaptic Ca(2+) signals, as well as neurotransmitter release, are significantly decreased in terminals containing mitochondria...
December 30, 2016: EMBO Reports
David Roy Smith
No abstract text is available yet for this article.
December 28, 2016: EMBO Reports
Bruno Polak, Patrik Risteski, Sonja Lesjak, Iva M Tolić
In the mitotic spindle, kinetochore microtubules form k-fibers, whereas overlap or interpolar microtubules form antiparallel arrays containing the cross-linker protein regulator of cytokinesis 1 (PRC1). We have recently shown that an overlap bundle, termed bridging fiber, links outermost sister k-fibers. However, the relationship between overlap bundles and k-fibers throughout the spindle remained unknown. Here, we show that in a metaphase spindle more than 90% of overlap bundles act as a bridge between sister k-fibers...
December 27, 2016: EMBO Reports
Tetsuo Kobayashi, Kosuke Nakazono, Mio Tokuda, Yu Mashima, Brian David Dynlacht, Hiroshi Itoh
Loss of primary cilia is frequently observed in tumor cells, including pancreatic ductal adenocarcinoma (PDAC) cells, suggesting that the absence of this organelle may promote tumorigenesis through aberrant signal transduction and the inability to exit the cell cycle. However, the molecular mechanisms that explain how PDAC cells lose primary cilia are still ambiguous. In this study, we found that inhibition or silencing of histone deacetylase 2 (HDAC2) restores primary cilia formation in PDAC cells. Inactivation of HDAC2 results in decreased Aurora A expression, which promotes disassembly of primary cilia...
December 27, 2016: EMBO Reports
Stepan Jerabek, Calista Kl Ng, Guangming Wu, Marcos J Arauzo-Bravo, Kee-Pyo Kim, Daniel Esch, Vikas Malik, Yanpu Chen, Sergiy Velychko, Caitlin M MacCarthy, Xiaoxiao Yang, Vlad Cojocaru, Hans R Schöler, Ralf Jauch
The transcription factor Oct4 is a core component of molecular cocktails inducing pluripotent stem cells (iPSCs), while other members of the POU family cannot replace Oct4 with comparable efficiency. Rather, group III POU factors such as Oct6 induce neural lineages. Here, we sought to identify molecular features determining the differential DNA-binding and reprogramming activity of Oct4 and Oct6. In enhancers of pluripotency genes, Oct4 cooperates with Sox2 on heterodimeric SoxOct elements. By re-analyzing ChIP-Seq data and performing dimerization assays, we found that Oct6 homodimerizes on palindromic OctOct more cooperatively and more stably than Oct4...
December 22, 2016: EMBO Reports
Zhibin Zhang, Yanan Liu, Hao Huang, Minghui Gao, Di Wu, Qing Kong, Yuelin Zhang
MAP kinase signaling is an integral part of plant immunity. Disruption of the MEKK1-MKK1/2-MPK4 kinase cascade results in constitutive immune responses mediated by the NLR protein SUMM2, but the molecular mechanism is so far poorly characterized. Here, we report that SUMM2 monitors a substrate protein of MPK4, CALMODULIN-BINDING RECEPTOR-LIKE CYTOPLASMIC KINASE 3 (CRCK3). Similar to SUMM2, CRCK3 was isolated from a suppressor screen of mkk1 mkk2 and is required for the autoimmunity phenotypes in mekk1, mkk1 mkk2, and mpk4 mutants...
December 16, 2016: EMBO Reports
Maria I Dauden, Jan Kosinski, Olga Kolaj-Robin, Ambroise Desfosses, Alessandro Ori, Celine Faux, Niklas A Hoffmann, Osita F Onuma, Karin D Breunig, Martin Beck, Carsten Sachse, Bertrand Séraphin, Sebastian Glatt, Christoph W Müller
The highly conserved eukaryotic Elongator complex performs specific chemical modifications on wobble base uridines of tRNAs, which are essential for proteome stability and homeostasis. The complex is formed by six individual subunits (Elp1-6) that are all equally important for its tRNA modification activity. However, its overall architecture and the detailed reaction mechanism remain elusive. Here, we report the structures of the fully assembled yeast Elongator and the Elp123 sub-complex solved by an integrative structure determination approach showing that two copies of the Elp1, Elp2, and Elp3 subunits form a two-lobed scaffold, which binds Elp456 asymmetrically...
December 14, 2016: EMBO Reports
Dheva T Setiaputra, Derrick Th Cheng, Shan Lu, Jesse M Hansen, Udit Dalwadi, Cindy Hy Lam, Jeffrey L To, Meng-Qiu Dong, Calvin K Yip
Elongator is a ~850 kDa protein complex involved in multiple processes from transcription to tRNA modification. Conserved from yeast to humans, Elongator is assembled from two copies of six unique subunits (Elp1 to Elp6). Despite the wealth of structural data on the individual subunits, the overall architecture and subunit organization of the full Elongator and the molecular mechanisms of how it exerts its multiple activities remain unclear. Using single-particle electron microscopy (EM), we revealed that yeast Elongator adopts a bilobal architecture and an unexpected asymmetric subunit arrangement resulting from the hexameric Elp456 subassembly anchored to one of the two Elp123 lobes that form the structural scaffold...
November 21, 2016: EMBO Reports
Thomas C Erren, J Valérie Groß, Ursula Wild, Philip Lewis, David M Shaw
No abstract text is available yet for this article.
January 2017: EMBO Reports
Ragna Sannerud, Wim Annaert
No abstract text is available yet for this article.
January 2017: EMBO Reports
Young Dong Yoo, Dae-Hee Lee, Hyunjoo Cha-Molstad, Hyungsin Kim, Su Ran Mun, Changhoon Ji, Seong Hye Park, Ki Sa Sung, Seung Ah Choi, Joonsung Hwang, Deric M Park, Seung-Ki Kim, Kyung-Jae Park, Shin-Hyuk Kang, Sang Cheul Oh, Aaron Ciechanover, Yong J Lee, Bo Yeon Kim, Yong Tae Kwon
Although proteasome inhibitors (PIs) are used as anticancer drugs to treat various cancers, their relative therapeutic efficacy on stem cells vs. bulk cancers remains unknown. Here, we show that stem cells derived from gliomas, GSCs, are up to 1,000-fold more sensitive to PIs (IC50, 27-70 nM) compared with their differentiated controls (IC50, 47 to »100 μM). The stemness of GSCs correlates to increased ubiquitination, whose misregulation readily triggers apoptosis. PI-induced apoptosis of GSCs is independent of NF-κB but involves the phosphorylation of c-Jun N-terminal kinase as well as the transcriptional activation of endoplasmic reticulum (ER) stress-associated proapoptotic mediators...
January 2017: EMBO Reports
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