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Nature Cell Biology

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https://www.readbyqxmd.com/read/28650479/aml1-eto-requires-enhanced-c-d-box-snorna-rnp-formation-to-induce-self-renewal-and-leukaemia
#1
Fengbiao Zhou, Yi Liu, Christian Rohde, Cornelius Pauli, Dennis Gerloff, Marcel Köhn, Danny Misiak, Nicole Bäumer, Chunhong Cui, Stefanie Göllner, Thomas Oellerich, Hubert Serve, Maria-Paz Garcia-Cuellar, Robert Slany, Jaroslaw P Maciejewski, Bartlomiej Przychodzen, Barbara Seliger, Hans-Ulrich Klein, Christoph Bartenhagen, Wolfgang E Berdel, Martin Dugas, Makoto Mark Taketo, Daneyal Farouq, Schraga Schwartz, Aviv Regev, Josée Hébert, Guy Sauvageau, Caroline Pabst, Stefan Hüttelmaier, Carsten Müller-Tidow
Leukaemogenesis requires enhanced self-renewal, which is induced by oncogenes. The underlying molecular mechanisms remain incompletely understood. Here, we identified C/D box snoRNAs and rRNA 2'-O-methylation as critical determinants of leukaemic stem cell activity. Leukaemogenesis by AML1-ETO required expression of the groucho-related amino-terminal enhancer of split (AES). AES functioned by inducing snoRNA/RNP formation via interaction with the RNA helicase DDX21. Similarly, global loss of C/D box snoRNAs with concomitant loss of rRNA 2'-O-methylation resulted in decreased leukaemia self-renewal potential...
June 26, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28628085/opa1-and-cardiolipin-team-up-for-mitochondrial-fusion
#2
Raymond Liu, David C Chan
Fusion between the inner membranes of two mitochondria requires the GTPase optic atrophy 1 (OPA1), but the molecular mechanism is poorly understood. A study now shows that fusion of two liposomes can be performed by OPA1 tethered to just one liposome, through an interaction with the phospholipid cardiolipin on the opposing liposome.
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28628084/long-term-imaging-of-cellular-forces-with-high-precision-by-elastic-resonator-interference-stress-microscopy
#3
Nils M Kronenberg, Philipp Liehm, Anja Steude, Johanna A Knipper, Jessica G Borger, Giuliano Scarcelli, Kristian Franze, Simon J Powis, Malte C Gather
Cellular forces are crucial for many biological processes but current methods to image them have limitations with respect to data analysis, resolution and throughput. Here, we present a robust approach to measure mechanical cell-substrate interactions in diverse biological systems by interferometrically detecting deformations of an elastic micro-cavity. Elastic resonator interference stress microscopy (ERISM) yields stress maps with exceptional precision and large dynamic range (2 nm displacement resolution over a >1 μm range, translating into 1 pN force sensitivity)...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28628083/molecular-basis-of-selective-mitochondrial-fusion-by-heterotypic-action-between-opa1-and-cardiolipin
#4
Tadato Ban, Takaya Ishihara, Hiroto Kohno, Shotaro Saita, Ayaka Ichimura, Katsumi Maenaka, Toshihiko Oka, Katsuyoshi Mihara, Naotada Ishihara
Mitochondria are highly dynamic organelles that undergo frequent fusion and fission. Optic atrophy 1 (OPA1) is an essential GTPase protein for both mitochondrial inner membrane (IM) fusion and cristae morphology. Under mitochondria-stress conditions, membrane-anchored L-OPA1 is proteolytically cleaved to form peripheral S-OPA1, leading to the selection of damaged mitochondria for mitophagy. However, molecular details of the selective mitochondrial fusion are less well understood. Here, we showed that L-OPA1 and cardiolipin (CL) cooperate in heterotypic mitochondrial IM fusion...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28628082/quantifying-forces-in-cell-biology
#5
REVIEW
Pere Roca-Cusachs, Vito Conte, Xavier Trepat
Cells exert, sense, and respond to physical forces through an astounding diversity of mechanisms. Here we review recently developed tools to quantify the forces generated by cells. We first review technologies based on sensors of known or assumed mechanical properties, and discuss their applicability and limitations. We then proceed to draw an analogy between these human-made sensors and force sensing in the cell. As mechanics is increasingly revealed to play a fundamental role in cell function we envisage that tools to quantify physical forces may soon become widely applied in life-sciences laboratories...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28628081/o-glcnacylation-of-fumarase-maintains-tumour-growth-under-glucose-deficiency
#6
Ting Wang, Qiujing Yu, Jingjie Li, Bin Hu, Qin Zhao, Chunmin Ma, Wenhua Huang, Lingang Zhuo, Houqin Fang, Lujian Liao, Y Eugene Chin, Yuhui Jiang
Chromatin-associated fumarase (FH) affects histone methylation via its metabolic activity. However, whether this effect is involved in gene transcription remains to be clarified. In this study, we show that under glucose deprivation conditions, AMPK phosphorylates FH at Ser75, which in turn forms a complex with ATF2 and participates in promoter activation. FH-catalysed fumarate in promoter regions inhibits KDM2A demethylase activity, and thus maintains the H3K36me2 profile and facilitates gene expression for cell growth arrest...
June 19, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28604678/dynamic-subunit-turnover-in-escrt-iii-assemblies-is-regulated-by-vps4-to-mediate-membrane-remodelling-during-cytokinesis
#7
Beata E Mierzwa, Nicolas Chiaruttini, Lorena Redondo-Morata, Joachim Moser von Filseck, Julia König, Jorge Larios, Ina Poser, Thomas Müller-Reichert, Simon Scheuring, Aurélien Roux, Daniel W Gerlich
The endosomal sorting complex required for transport (ESCRT)-III mediates membrane fission in fundamental cellular processes, including cytokinesis. ESCRT-III is thought to form persistent filaments that over time increase their curvature to constrict membranes. Unexpectedly, we found that ESCRT-III at the midbody of human cells rapidly turns over subunits with cytoplasmic pools while gradually forming larger assemblies. ESCRT-III turnover depended on the ATPase VPS4, which accumulated at the midbody simultaneously with ESCRT-III subunits, and was required for assembly of functional ESCRT-III structures...
June 12, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28604677/pramel7-mediates-ground-state-pluripotency-through-proteasomal-epigenetic-combined-pathways
#8
Urs Graf, Elisa A Casanova, Sarah Wyck, Damian Dalcher, Marco Gatti, Eva Vollenweider, Michal J Okoniewski, Fabienne A Weber, Sameera S Patel, Marc W Schmid, Jiwen Li, Jafar Sharif, Guido A Wanner, Haruhiko Koseki, Jiemin Wong, Pawel Pelczar, Lorenza Penengo, Raffaella Santoro, Paolo Cinelli
Naive pluripotency is established in preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of naive pluripotency. 2i culture has optimized this state, leading to a gene signature and DNA hypomethylation closely comparable to preimplantation epiblast, the developmental ground state. Here we show that Pramel7 (PRAME-like 7), a protein highly expressed in the inner cell mass (ICM) but expressed at low levels in ESCs, targets for proteasomal degradation UHRF1, a key factor for DNA methylation maintenance...
June 12, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28604676/cholesterol-and-fatty-acids-regulate-cysteine-ubiquitylation-of-acat2-through-competitive-oxidation
#9
Yong-Jian Wang, Yan Bian, Jie Luo, Ming Lu, Ying Xiong, Shu-Yuan Guo, Hui-Yong Yin, Xu Lin, Qin Li, Catherine C Y Chang, Ta-Yuan Chang, Bo-Liang Li, Bao-Liang Song
Ubiquitin linkage to cysteine is an unconventional modification targeting protein for degradation. However, the physiological regulation of cysteine ubiquitylation is still mysterious. Here we found that ACAT2, a cellular enzyme converting cholesterol and fatty acid to cholesteryl esters, was ubiquitylated on Cys277 for degradation when the lipid level was low. gp78-Insigs catalysed Lys48-linked polyubiquitylation on this Cys277. A high concentration of cholesterol and fatty acid, however, induced cellular reactive oxygen species (ROS) that oxidized Cys277, resulting in ACAT2 stabilization and subsequently elevated cholesteryl esters...
June 12, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28581477/inter-organ-signalling-by-hrg-7-promotes-systemic-haem-homeostasis
#10
Jason Sinclair, Katherine Pinter, Tamika Samuel, Simon Beardsley, Xiaojing Yuan, Jianbing Zhang, Kevin Meng, Sijung Yun, Michael Krause, Iqbal Hamza
Growing evidence in vertebrates predicts that cellular haem levels in animals are maintained not only by a cell's internal capacity for haem synthesis in a cell-autonomous manner, but also by an inter-organ haem trafficking network through cell-non-autonomous regulation. Using Caenorhabditis elegans, a genetically and optically amenable animal model for visualizing haem-dependent signalling, we show that HRG-7, a protein with homology to aspartic proteases, mediates inter-organ signalling between the intestine and extra-intestinal tissues...
June 5, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28581476/lgr5-expressing-chief-cells-drive-epithelial-regeneration-and-cancer-in-the-oxyntic-stomach
#11
Marc Leushacke, Si Hui Tan, Angeline Wong, Yada Swathi, Amin Hajamohideen, Liang Thing Tan, Jasmine Goh, Esther Wong, Simon L I J Denil, Kazuhiro Murakami, Nick Barker
The daily renewal of the corpus epithelium is fuelled by adult stem cells residing within tubular glands, but the identity of these stem cells remains controversial. Lgr5 marks homeostatic stem cells and 'reserve' stem cells in multiple tissues. Here, we report Lgr5 expression in a subpopulation of chief cells in mouse and human corpus glands. Using a non-variegated Lgr5-2A-CreERT2 mouse model, we show by lineage tracing that Lgr5-expressing chief cells do not behave as corpus stem cells during homeostasis, but are recruited to function as stem cells to effect epithelial renewal following injury by activating Wnt signalling...
June 5, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28553938/the-mbnl3-splicing-factor-promotes-hepatocellular-carcinoma-by-increasing-pxn-expression-through-the-alternative-splicing-of-lncrna-pxn-as1
#12
Ji-Hang Yuan, Xiao-Ning Liu, Tian-Tian Wang, Wei Pan, Qi-Fei Tao, Wei-Ping Zhou, Fang Wang, Shu-Han Sun
Understanding the roles of splicing factors and splicing events during tumorigenesis would open new avenues for targeted therapies. Here we identify an oncofetal splicing factor, MBNL3, which promotes tumorigenesis and indicates poor prognosis of hepatocellular carcinoma patients. MBNL3 knockdown almost completely abolishes hepatocellular carcinoma tumorigenesis. Transcriptomic analysis revealed that MBNL3 induces lncRNA-PXN-AS1 exon 4 inclusion. The transcript lacking exon 4 binds to coding sequences of PXN mRNA, causes dissociation of translation elongation factors from PXN mRNA, and thereby inhibits PXN mRNA translation...
May 29, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28446817/shh-mediated-centrosomal-recruitment-of-pka-promotes-symmetric-proliferative-neuroepithelial-cell%C3%A2-division
#13
Murielle Saade, Elena Gonzalez-Gobartt, Rene Escalona, Susana Usieto, Elisa Martí
Tight control of the balance between self-expanding symmetric and self-renewing asymmetric neural progenitor divisions is crucial to regulate the number of cells in the developing central nervous system. We recently demonstrated that Sonic hedgehog (Shh) signalling is required for the expansion of motor neuron progenitors by maintaining symmetric divisions. Here we show that activation of Shh/Gli signalling in dividing neuroepithelial cells controls the symmetric recruitment of PKA to the centrosomes that nucleate the mitotic spindle, maintaining symmetric proliferative divisions...
April 27, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28553939/linking-e-cadherin-mechanotransduction-to-cell-metabolism-through-force-mediated-activation-of%C3%A2-ampk
#14
Jennifer L Bays, Hannah K Campbell, Christy Heidema, Michael Sebbagh, Kris A DeMali
The response of cells to mechanical force is a major determinant of cell behaviour and is an energetically costly event. How cells derive energy to resist mechanical force is unknown. Here, we show that application of force to E-cadherin stimulates liver kinase B1 (LKB1) to activate AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. LKB1 recruits AMPK to the E-cadherin mechanotransduction complex, thereby stimulating actomyosin contractility, glucose uptake and ATP production. The increase in ATP provides energy to reinforce the adhesion complex and actin cytoskeleton so that the cell can resist physiological forces...
June 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28553937/stem-cell-plasticity-enables-hair-regeneration-following-lgr5-cell-loss
#15
Joerg D Hoeck, Brian Biehs, Antonina V Kurtova, Noelyn M Kljavin, Felipe de Sousa E Melo, Bruno Alicke, Hartmut Koeppen, Zora Modrusan, Robert Piskol, Frederic J de Sauvage
Under injury conditions, dedicated stem cell populations govern tissue regeneration. However, the molecular mechanisms that induce stem cell regeneration and enable plasticity are poorly understood. Here, we investigate stem cell recovery in the context of the hair follicle to understand how two molecularly distinct stem cell populations are integrated. Utilizing diphtheria-toxin-mediated cell ablation of Lgr5(+) (leucine-rich repeat-containing G-protein-coupled receptor 5) stem cells, we show that killing of Lgr5(+) cells in mice abrogates hair regeneration but this is reversible...
June 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28530660/endoglin-prevents-vascular-malformation-by-regulating-flow-induced-cell-migration-and-specification-through-vegfr2-signalling
#16
Yi Jin, Lars Muhl, Mikhail Burmakin, Yixin Wang, Anne-Claire Duchez, Christer Betsholtz, Helen M Arthur, Lars Jakobsson
Loss-of-function (LOF) mutations in the endothelial cell (EC)-enriched gene endoglin (ENG) cause the human disease hereditary haemorrhagic telangiectasia-1, characterized by vascular malformations promoted by vascular endothelial growth factor A (VEGFA). How ENG deficiency alters EC behaviour to trigger these anomalies is not understood. Mosaic ENG deletion in the postnatal mouse rendered Eng LOF ECs insensitive to flow-mediated venous to arterial migration. Eng LOF ECs retained within arterioles acquired venous characteristics and secondary ENG-independent proliferation resulting in arteriovenous malformation (AVM)...
June 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28530659/actin-cortex-architecture-regulates-cell-surface-tension
#17
Priyamvada Chugh, Andrew G Clark, Matthew B Smith, Davide A D Cassani, Kai Dierkes, Anan Ragab, Philippe P Roux, Guillaume Charras, Guillaume Salbreux, Ewa K Paluch
Animal cell shape is largely determined by the cortex, a thin actin network underlying the plasma membrane in which myosin-driven stresses generate contractile tension. Tension gradients result in local contractions and drive cell deformations. Previous cortical tension regulation studies have focused on myosin motors. Here, we show that cortical actin network architecture is equally important. First, we observe that actin cortex thickness and tension are inversely correlated during cell-cycle progression. We then show that the actin filament length regulators CFL1, CAPZB and DIAPH1 regulate mitotic cortex thickness and find that both increasing and decreasing thickness decreases tension in mitosis...
June 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28530658/endoglin-controls-blood-vessel-diameter-through-endothelial-cell-shape-changes-in-response-to-haemodynamic-cues
#18
Wade W Sugden, Robert Meissner, Tinri Aegerter-Wilmsen, Roman Tsaryk, Elvin V Leonard, Jeroen Bussmann, Mailin J Hamm, Wiebke Herzog, Yi Jin, Lars Jakobsson, Cornelia Denz, Arndt F Siekmann
The hierarchical organization of properly sized blood vessels ensures the correct distribution of blood to all organs of the body, and is controlled via haemodynamic cues. In current concepts, an endothelium-dependent shear stress set point causes blood vessel enlargement in response to higher flow rates, while lower flow would lead to blood vessel narrowing, thereby establishing homeostasis. We show that during zebrafish embryonic development increases in flow, after an initial expansion of blood vessel diameters, eventually lead to vessel contraction...
June 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28530657/normal-and-cancerous-mammary-stem-cells-evade-interferon-induced-constraint-through-the-mir-199a-lcor-axis
#19
Toni Celià-Terrassa, Daniel D Liu, Abrar Choudhury, Xiang Hang, Yong Wei, Jose Zamalloa, Raymundo Alfaro-Aco, Rumela Chakrabarti, Yi-Zhou Jiang, Bong Ihn Koh, Heath A Smith, Christina DeCoste, Jun-Jing Li, Zhi-Ming Shao, Yibin Kang
Tumour-initiating cells, or cancer stem cells (CSCs), possess stem-cell-like properties observed in normal adult tissue stem cells. Normal and cancerous stem cells may therefore share regulatory mechanisms for maintaining self-renewing capacity and resisting differentiation elicited by cell-intrinsic or microenvironmental cues. Here, we show that miR-199a promotes stem cell properties in mammary stem cells and breast CSCs by directly repressing nuclear receptor corepressor LCOR, which primes interferon (IFN) responses...
June 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28504708/receptor-oligomerization-guides-pathway-choice-between-proteasomal-and-autophagic-degradation
#20
Kefeng Lu, Fabian den Brave, Stefan Jentsch
Abnormal or aggregated proteins have a strong cytotoxic potential and are causative for human disorders such as Alzheimer's, Parkinson's, Huntington's disease and amyotrophic lateral sclerosis. If not restored by molecular chaperones, abnormal proteins are typically degraded by proteasomes or eliminated by selective autophagy. The discovery that both pathways are initiated by substrate ubiquitylation but utilize different ubiquitin receptors incited a debate over how pathway choice is achieved. Here, we demonstrate in yeast that pathway choice is made after substrate ubiquitylation by competing ubiquitin receptors harbouring either proteasome- or autophagy-related protein 8 (Atg8/LC3)-binding modules...
June 2017: Nature Cell Biology
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