Articles

Global analysis of X-chromosome dosage compensation

Drosophila melanogaster females have two X chromosomes and two autosome sets (XX;AA), while males have a single X chromosome and two autosome sets (X;AA). Drosophila male somatic cells compensate for a single cop...

Authors: Vaijayanti Gupta, Michael Parisi, David Sturgill, Rachel Nuttall, Michael Doctolero, Olga K Dudko, James D Malley, P Scott Eastman and Brian Oliver

Recycling signals in the neural crest

Vertebrate neural crest cells are multipotent and differentiate into structures that include cartilage and the bones of the face, as well as much of the peripheral nervous system. Understanding how different m...

Authors: Lisa A Taneyhill and Marianne Bronner-Fraser

Compound developmental eye disorders following inactivation of TGFβ signaling in neural-crest stem cells

Development of the eye depends partly on the periocular mesenchyme derived from the neural crest (NC), but the fate of NC cells in mammalian eye development and the signals coordinating the formation of ocular...

Authors: Lars M Ittner, Heiko Wurdak, Kerstin Schwerdtfeger, Thomas Kunz, Fabian Ille, Per Leveen, Tord A Hjalt, Ueli Suter, Stefan Karlsson, Farhad Hafezi, Walter Born and Lukas Sommer

Guanine-nucleotide exchange on ribosome-bound elongation factor G initiates the translocation of tRNAs

During the translation of mRNA into polypeptide, elongation factor G (EF-G) catalyzes the translocation of peptidyl-tRNA from the A site to the P site of the ribosome. According to the 'classical' model, EF-G ...

Authors: Andrey V Zavialov, Vasili V Hauryliuk and Måns Ehrenberg

Movement in ribosome translocation

Translocation of peptidyl-tRNA and mRNA within the ribosome during protein synthesis is promoted by the elongation factor EF-G and by the hydrolysis of GTP. A new study reports that EF-G binds to ribosomes as ...

Authors: Christopher S Fraser and John WB Hershey

The GTPase switch in ribosomal translocation

Information from careful measurements of the affinity of ribosome-associated proteins for GTP and GDP, and from structural analyses, suggests that elongation factor-G must assume three different structures dur...

Authors: Pete Moore

Untangling the web of functional and physical interactions in yeast

An analysis of an integrated network of over 150,000 functional and physical interactions in yeast suggests that the network can be hierarchically decomposed into themes and thematic maps. This decomposition c...

Authors: Markus J Herrgård and Bernhard Ø Palsson

Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiaeinteraction network

Large-scale studies have revealed networks of various biological interaction types, such as protein-protein interaction, genetic interaction, transcriptional regulation, sequence homology, and expression corre...

Authors: Lan V Zhang, Oliver D King, Sharyl L Wong, Debra S Goldberg, Amy HY Tong, Guillaume Lesage, Brenda Andrews, Howard Bussey, Charles Boone and Frederick P Roth

A road map of yeast interactions

Analysis of a yeast network that integrates five interaction datasets reveals the presence of large topological structures reflecting biological themes.

Authors: Jonathan B Weitzman

Dishevelled and Wnt signaling: is the nucleus the final frontier?

The phosphoprotein Dishevelled (Dsh) is an essential component of Wnt signaling pathways and transduces signals into three separate branches, the canonical, non-canonical and Ca²⁺ pathways. How Dsh focuses signal...

Authors: Raymond Habas and Igor B Dawid

Dishevelled nuclear shuttling

Structure-function analysis of the Dishevelled (Dsh) protein in frog embryos has defined sequences that regulate Dsh nuclear localization, which proves critical for Wnt signaling.

Authors: Jonathan B Weitzman

Nuclear localization is required for Dishevelled function in Wnt/β-catenin signaling

Dishevelled (Dsh) is a key component of multiple signaling pathways that are initiated by Wnt secreted ligands and Frizzled receptors during embryonic development. Although Dsh has been detected in a number of...

Authors: Keiji Itoh, Barbara K Brott, Gyu-Un Bae, Marianne J Ratcliffe and Sergei Y Sokol

All systems GO for understanding mouse gene function

It is widely supposed that the tissue specificity of gene expression indicates gene function. Now, an extensive analysis of gene expression in the mouse reveals that quantitative measurement of expression leve...

Authors: Chris Holmes and Steve DM Brown

The functional landscape of mouse gene expression

Large-scale quantitative analysis of transcriptional co-expression has been used to dissect regulatory networks and to predict the functions of new genes discovered by genome sequencing in model organisms such...

Authors: Wen Zhang, Quaid D Morris, Richard Chang, Ofer Shai, Malina A Bakowski, Nicholas Mitsakakis, Naveed Mohammad, Mark D Robinson, Ralph Zirngibl, Eszter Somogyi, Nancy Laurin, Eftekhar Eftekharpour, Eric Sat, Jörg Grigull, Qun Pan, Wen-Tao Peng…

Co-regulation of mouse genes predicts function

Large-scale microarray analyses reveal that transcriptional co-regulation patterns can be remarkably helpful in predicting the function of novel mouse genes.

Authors: Jonathan B Weitzman

Editorial

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Who's driving the centromere?

Centromere function is remarkably conserved between species, yet the satellite sequences that make up centromeric DNA are highly divergent. Proteins that bind these sequences appear to be evolving under positi...

Authors: Gregory P Copenhaver

The curious world of apoptotic cell clearance

Analysis of knockout mice has brought into question the previously proposed role of the phosphatidylserine receptor (Ptdsr) in the clearance of apoptotic cell corpses, and has suggested important functions in ...

Authors: Jonathan B Weitzman

Hide and seek: the secret identity of the phosphatidylserine receptor

Phosphatidylserine on the dying cell surface helps identify apoptotic cells to phagocytes, which then engulf them. A candidate phagocyte receptor for phosphatidylserine was identified using phage display, but ...

Authors: Patrick Williamson and Robert A Schlegel

Adaptive evolution of centromere proteins in plants and animals

Centromeres represent the last frontiers of plant and animal genomics. Although they perform a conserved function in chromosome segregation, centromeres are typically composed of repetitive satellite sequences...

Authors: Paul B Talbert, Terri D Bryson and Steven Henikoff

Making sense of centromeres

Comparative analysis of the proteins that bind exclusively at the centromere provides evidence of an evolutionary battle that may make sense of sex.

Authors: Pete Moore

The phosphatidylserine receptor has essential functions during embryogenesis but not in apoptotic cell removal

Phagocytosis of apoptotic cells is fundamental to animal development, immune function and cellular homeostasis. The phosphatidylserine receptor (Ptdsr) on phagocytes has been implicated in the recognition and ...

Authors: Jens Böse, Achim D Gruber, Laura Helming, Stefanie Schiebe, Ivonne Wegener, Martin Hafner, Marianne Beales, Frank Köntgen and Andreas Lengeling

Wnt signaling and the developmental fate of lung cells

Constitutive activation of the Wnt signaling pathway during lung development in mouse embryos causes some cells to develop a gut-like phenotype. These findings are reminiscent of classical embryological experi...

Authors: Julie Clayton

Hyperactive Wnt signaling changes the developmental potential of embryonic lung endoderm

Studies in many model systems have shown that canonical signaling through the pathway downstream of ligands of the Wnt family can regulate multiple steps in organogenesis, including cell proliferation, differe...

Authors: Tadashi Okubo and Brigid LM Hogan

Intestine in the lung

The phenomenon of metaplasia, in which one tissue type is converted into another, is beginning to be explained in molecular terms. The transformation of lung to intestinal tissue has not previously been descri...

Authors: Jonathan MW Slack

Editorial

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The hydrodynamics of dolphin drafting

Drafting in cetaceans is defined as the transfer of forces between individuals without actual physical contact between them. This behavior has long been surmised to explain how young dolphin calves keep up wit...

Authors: Daniel Weihs

Hitching a lift hydrodynamically - in swimming, flying and cycling

Swimming animals set the water around them moving, and flying animals generate air movements. Other animals traveling with them can save energy by exploiting these movements of the fluid medium; similarly, a c...

Authors: R McNeill Alexander

Examining dolphin hydrodynamics provides clues to calf-loss during tuna fishing

A combination of mathematical modeling and direct observation of the swimming behavior of dolphin mother-calf pairs has shown how the calf can gain much of the energy required for swimming if it is positioned ...

Authors: Pete Moore

Editorial

Authors: Theodora Bloom

Bending out and breaking away: host-cell accomplices in retroviral escape

Budding through the host-cell membrane is a key step in the life cycle of many viruses. Recent studies of retrovirus replication implicate a large number of cellular proteins in this process.

Authors: Melvyn W Yap and Jonathan P Stoye

Budding viral hijackers co-opt the endocytic machinery to make a getaway

A retroviral Gag protein interacts with a cellular protein involved in forming endocytic vesicles in a manner that affects the production of virus particles. These findings help define the suite of host-cell c...

Authors: Diane Martindale

Endophilins interact with Moloney murine leukemia virus Gag and modulate virion production

The retroviral Gag protein is the central player in the process of virion assembly at the plasma membrane, and is sufficient to induce the formation and release of virus-like particles. Recent evidence suggest...

Authors: Margaret Q Wang, Wankee Kim, Guangxia Gao, Ted A Torrey, Herbert C Morse III, Pietro De Camilli and Stephen P Goff

RNAi and the shape of things to come

A large-scale screen in Drosophila cells has shown how RNA interference can provide insights into the pathways controlling cell morphology.

Authors: Jonathan B Weitzman

Connecting LKB1 and AMPK links metabolism with cancer

The tumor suppressor gene product LKB1 has been identified as the upstream activating kinase for the stress-responsive AMP-activated kinase, providing a link between regulators of cellular metabolism and cell ...

Authors: Pete Moore

At the crossroads: AMP-activated kinase and the LKB1 tumor suppressor link cell proliferation to metabolic regulation

The tumor suppressor kinase LKB1 has been identified as a physiologic activator of the key metabolic regulator 5'-AMP-activated protein kinase, establishing a possible molecular link between the regulation of ...

Authors: John M Kyriakis

Editorial

Authors: Theodora Bloom

A functional genomic analysis of cell morphology using RNA interference

The diversity of metazoan cell shapes is influenced by the dynamic cytoskeletal network. With the advent of RNA-interference (RNAi) technology, it is now possible to screen systematically for genes controlling...

Authors: AA Kiger, B Baum, S Jones, MR Jones, A Coulson, C Echeverri and N Perrimon

Functional genomics of cell morphology using RNA interference: pick your style, broad or deep

Several new studies have used RNA interference to screen for protein functions affecting cell shape, mitosis and cytokinesis of Drosophila cells in culture. One broad survey of nearly 1,000 proteins and three stu...

Authors: Thomas D Pollard

Complexes between the LKB1 tumor suppressor, STRADα/β and MO25α/β are upstream kinases in the AMP-activated protein kinase cascade

The AMP-activated protein kinase (AMPK) cascade is a sensor of cellular energy charge that acts as a 'metabolic master switch' and inhibits cell proliferation. Activation requires phosphorylation of Thr172 of ...

Authors: Simon A Hawley, Jérôme Boudeau, Jennifer L Reid, Kirsty J Mustard, Lina Udd, Tomi P Mäkelä, Dario R Alessi and D Grahame Hardie

Identifying new T-cell regulators

Functional genomic screening for new components of the signaling pathway that is triggered when T cells are activated has identified novel signaling molecules that are potential drug targets.

Authors: Diane Martindale

Systematic identification of regulatory proteins critical for T-cell activation

The activation of T cells, mediated by the T-cell receptor (TCR), activates a battery of specific membrane-associated, cytosolic and nuclear proteins. Identifying the signaling proteins downstream of TCR activ...

Authors: Peter Chu, Jorge Pardo, Haoran Zhao, Connie C Li, Erlina Pali, Mary M Shen, Kunbin Qu, Simon X Yu, Betty CB Huang, Peiwen Yu, Esteban S Masuda, Susan M Molineaux, Frank Kolbinger, Gregorio Aversa, Jan de Vries, Donald G Payan…

Shrinkage control: regulation of insulin-mediated growth by FOXO transcription factors

The insulin signaling pathway regulates organismal growth in response to nutrient conditions by controlling a range of metabolic and biosynthetic processes. Recent studies in Drosophila have shown how transcripti...

Authors: Thomas P Neufeld

Controlling how many cells make a fly

Studies in Drosophila have revealed the Forkhead-family transcription factor FOXO to be a crucial mediator of the branch of the insulin-signaling pathway that controls cell number.

Authors: Pete Moore

The Drosophila Forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling

Forkhead transcription factors belonging to the FOXO subfamily are negatively regulated by protein kinase B (PKB) in response to signaling by insulin and insulin-like growth factor in Caenorhabditis elegans and m...

Authors: Martin A Jünger, Felix Rintelen, Hugo Stocker, Jonathan D Wasserman, Mátyás Végh, Thomas Radimerski, Michael E Greenberg and Ernst Hafen

Stress, sex and evolution

Despite the widespread view that the effects of mutations are exacerbated by environmental stresses, some stresses have been found to alleviate the effects of mutations in bacteria.

Authors: Pete Moore

Environmental stress and the effects of mutation

Mutations are the ultimate fuel for evolution, but most mutations have a negative effect on fitness. It has been widely accepted that these deleterious fitness effects are, on average, magnified in stressful e...

Authors: Santiago F Elena and J Arjan GM de Visser

Tracking evolution's footprints in the genome

The strategy of using 'phylogenetic footprinting' to find regulatory sites that are conserved between pairs of related complex genomes has led to the development of a suite of computational tools that succeed ...

Authors: Jonathan B Weitzman

Of mice and men: phylogenetic footprinting aids the discovery of regulatory elements

Phylogenetic footprinting is an approach to finding functionally important sequences in the genome that relies on detecting their high degrees of conservation across different species. A new study shows how mu...

Authors: Zhaolei Zhang and Mark Gerstein

Environmental stresses can alleviate the average deleterious effect of mutations

Fundamental questions in evolutionary genetics, including the possible advantage of sexual reproduction, depend critically on the effects of deleterious mutations on fitness. Limited existing experimental evid...

Authors: Roy Kishony and Stanislas Leibler