Nature Cell Biology contents: April 2013 Volume 15 Number 4, pp 337 - 441

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Abstracts due 31 May, Register by 21 June   Advertisement Nature Structural & Molecular Biology FOCUS ON EPIGENETIC DYNAMICS This Focus explores emerging themes and the functional implications of epigenetic dynamics. Access the Focus for FREE at: www.nature.com/nsmb/focus/epigeneticdynamics This Focus is freely available thanks to support from Active Motif   Turning Points Top GTPase switch: Ras then Rho and Rac   p337 Anne Ridley doi:10.1038/ncb2716 Perspective Top Cancer stem cells: The challenges ahead   pp338 - 344 Jan Paul Medema doi:10.1038/ncb2717 Cancer stem cells (CSCs) have been proposed as the driving force of tumorigenesis and the seeds of metastases. However, their existence and role remain a topic of intense debate. Recently, the identification of CSCs in endogenously developing mouse tumours has provided further support for this concept. Here I discuss the challenges in identifying CSCs, their dependency on a supportive niche and their role in metastasis, and propose that stemness is a flexible — rather than fixed — quality of tumour cells that can be lost and gained. News and Views Top Formin' cables under stress   pp345 - 346 Deborah Leckband doi:10.1038/ncb2715 How application of force affects actin remodelling during mechanotransduction has remained unclear. Mechanical manipulation of the cell cortex is now shown to trigger actin monomer release from filaments, which in turn activates formin-dependent actin filament elongation. This force-sensitive actin polymerization does not require GTPases or membrane receptors, but it involves actin itself. See also: Article by Higashida et al. Cullin' PLK1 from kinetochores   pp347 - 348 Colleen A. McGourty and Michael Rape doi:10.1038/ncb2722 To ensure proper attachment of all chromosomes to the spindle, PLK1 has to associate with kinetochores during prometaphase and must be released from these sites before sister chromatid separation can begin. The monoubiquitylation of PLK1 by the ubiquitin ligase CUL3-KLHL22 is now identified as a critical step in promoting the release of PLK1 from kinetochores, pushing non-proteolytic ubiquitylation into the limelight of cell division research. See also: Article by Beck et al. Polycomb complex recruitment in pluripotent stem cells   pp348 - 350 Maria J. Barrero and Juan Carlos Izpisua Belmonte doi:10.1038/ncb2723 The recruitment of the silencing complex Polycomb group (PcG) to its target sites in mammalian cells has remained elusive. A prevalent model proposes that the PRC1 component is recruited through recognition of methylated H3K27 found at target sites occupied by the PRC2 component. However, mounting evidence suggests that PRC2-independent mechanisms of PRC1 recruitment exist. Three studies describe that the histone demethylase Kdm2b binds to unmethylated CpG islands and recruits a subset of PRC1 complexes to chromatin in pluripotent stem cells. See also: Article by He et al. Research Highlights A STUbL in telomere protection | Blood cells: Each to their own niche | mTOR regulates pyrimidine synthesis | A jagged road to cancer stem cells Cell Biology JOBS of the week Lecturer / Associate Professor in Stem Cell Biology and Regenerative Medicine University of Reading Postdoctoral Associate in Cell Biology / Molecular Virology The Scripps Research Institute PhD Fellowships in Molecular Cell Biology Max Planck Institute of Molecular Physiology Two Lectureships / Senior Lectureships in Cell and Molecular Biology Queen Mary University of London Postdoc position in Cell- and Computational Biology CellNetworks - Dr. Ulrike Engel, Heidelberg University, Dr. Francois Nedelec, EMBL More Science jobs from Cell Biology EVENT Computational Cell Biology 23rd July - 12th August 2013 Cold Spring Harbor, United States More science events from Advertisement Labguru Research and Lab Management Software Manage research projects and lab logistics with Labguru web-based software. Enjoy easy access to current research projects and view your entire research history, including experiments, protocols, orders, specimens and more. Purchase an annual account and get an additional 2 months FREE. To learn more, go to www.labguru.com/nature   Articles Top Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation   pp353 - 362 Karin Klauke, Višnja Radulović, Mathilde Broekhuis, Ellen Weersing, Erik Zwart, Sandra Olthof, Martha Ritsema, Sophia Bruggeman, Xudong Wu, Kristian Helin, Leonid Bystrykh and Gerald de Haan doi:10.1038/ncb2701 Self-renewal and differentiation of adult stem cells ensures tissue homeostasis. De Haan and colleagues find that the chromatin-associated polycomb protein Cbx7 ensures self-renewal of haematopoietic stem cells (HSCs), whereas other polycomb proteins, such as Cbx8, induce differentiation. They find that although genes targeted by Cbx8 are highly expressed in HSCs and repressed in progenitors, Cbx7 target genes have the opposite expression pattern. Characterization of transcriptional networks in blood stem and progenitor cells using high-throughput single-cell gene expression analysis   pp363 - 372 Victoria Moignard, Iain C. Macaulay, Gemma Swiers, Florian Buettner, Judith Schütte, Fernando J. Calero-Nieto, Sarah Kinston, Anagha Joshi, Rebecca Hannah, Fabian J. Theis, Sten Eirik Jacobsen, Marella F. de Bruijn and Berthold Göttgens doi:10.1038/ncb2709 Gottgens and colleagues have analysed the expression of 18 haematopoietic factors in single primary blood and progenitor cells from mouse bone marrow. They delineate distinct states of expression for these transcription factors and identify regulatory relationships between the key factors Gata2, Gfi1 and Gfi2. Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes   pp373 - 384 Jin He, Li Shen, Ma Wan, Olena Taranova, Hao Wu and Yi Zhang doi:10.1038/ncb2702 How polycomb group proteins are recruited to lineage specific genes to repress their expression in mouse embryonic stem cells has been unclear. Zhang and colleagues show that the histone lysine demethylase Kdm2b recruits Ring1 of the PRC1 complex to a subset of these targets, through a non-catalytic domain. The expression of Kdm2 is also shown to be regulated by the pluripotency factors Oct4 and Sox2. See also: News and Views by Barrero & Belmonte C/EBPa controls acquisition and maintenance of adult haematopoietic stem cell quiescence   pp385 - 394 Min Ye, Hong Zhang, Giovanni Amabile, Henry Yang, Philipp B. Staber, Pu Zhang, Elena Levantini, Meritxell Alberich-Jordà, Junyan Zhang, Akira Kawasaki and Daniel G. Tenen doi:10.1038/ncb2698 How the characteristic quiescent status of adult HSCs is maintained is not well understood. Tenen and colleagues show that the transcription factor C/EBP is required to maintain a low proliferation rate in adult HSCs, partly through N-Myc repression. F- and G-actin homeostasis regulates mechanosensitive actin nucleation by formins   pp395 - 405 Chiharu Higashida, Tai Kiuchi, Yushi Akiba, Hiroaki Mizuno, Masahiro Maruoka, Shuh Narumiya, Kensaku Mizuno and Naoki Watanabe doi:10.1038/ncb2693 Watanabe and colleagues show that an increase in cytosolic G-actin levels following mechanical stress promotes Ca2+- and kinase-signalling-independent nucleation of actin filaments by formins. See also: News and Views by Leckband mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6    pp406 - 416 Francesca Nazio, Flavie Strappazzon, Manuela Antonioli, Pamela Bielli, Valentina Cianfanelli, Matteo Bordi, Christine Gretzmeier, Joern Dengjel, Mauro Piacentini, Gian Maria Fimia and Francesco Cecconi doi:10.1038/ncb2708 mTOR inhibition induces autophage-mediated degradation but few mTOR targets in the process have been identified so far. Cecconi and colleagues show that mTOR inhibits the autophagy regulator AMBRA1 by phosphorylation. Following autophagy induction, AMBRA1 is dephosphorylated and interacts with the E3 ligase TRAF6 to stabilize and activate ULK1 (a kinase required for autophagy) through its ubiquitylation. PtdIns(4)P regulates retromer–motor interaction to facilitate dynein–cargo dissociation at the trans-Golgi network   pp417 - 429 Yang Niu, Cheng Zhang, Zhe Sun, Zhi Hong, Ke Li, Demeng Sun, Yanrui Yang, Changlin Tian, Weimin Gong and Jia-Jia Liu doi:10.1038/ncb2710 How the interaction between molecular motors and cargoes is regulated is not well understood. Liu and colleagues show that phosphatidylinositol-4-phosphate (PtdIns(4)P) dissociates the retromer component sorting nexin SNX6 from the p150Glued subunit of dynactin on retrograde transport vesicles docking at the trans-Golgi network. PtdIns(4)P is also shown to modulate the association of SNX4 and dynein on retrograde vesicles en route to the endocytic pathway. Ubiquitylation-dependent localization of PLK1 in mitosis   pp430 - 439 Jochen Beck, Sarah Maerki, Markus Posch, Thibaud Metzger, Avinash Persaud, Hartmut Scheel, Kay Hofmann, Daniela Rotin, Patrick Pedrioli, Jason R. Swedlow, Matthias Peter and Izabela Sumara doi:10.1038/ncb2695 The dynamic localization of PLK1 to kinetochores is required for faithful chromosome segregation. Peter, Sumara and colleagues demonstrate that a KHL22-containing E3 ligase mediates degradation-independent removal of PLK1 from kinetochores to ensure satisfaction of the spindle assembly checkpoint and proper mitotic progression. See also: News and Views by McGourty & Rape Corrigenda Top Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin   p440 Lihua Min, Yuan Ji, Latifa Bakiri, Zhixin Qiu, Jin Cen, Xiaotao Chen, Lingli Chen, Harald Scheuch, Hai Zheng, Lunxiu Qin, Kurt Zatloukal, Lijian Hui and Erwin F. Wagner doi:10.1038/ncb2726 Nuclear transport factor directs localization of protein synthesis during mitosis   p441 Geert van den Bogaart, Anne C. Meinema, Victor Krasnikov, Liesbeth M. Veenhoff and Bert Poolman doi:10.1038/ncb2728 Top Advertisement Nature Medicine and Helmholtz Zentrum München present: 1st Annual Helmholtz-Nature Medicine Diabetes Conference September 22-24, 2013 Residenz München Munich, Germany Click here for more information or to register for this conference today!   Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. 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