Showing papers in "Nature Reviews Molecular Cell Biology in 2002"
TL;DR: It is clear that the understanding of the myofibroblast — its origins, functions and molecular regulation — will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
Abstract: During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
3,836 citations
TL;DR: The signal transducer and activator of transcription (STAT) proteins are among the most well studied of the latent cytoplasmic signal-dependent transcription-factor pathways.
Abstract: Extracellular proteins bound to cell-surface receptors can change nuclear gene expression patterns in minutes, with far-reaching consequences for development, cell growth and homeostasis. The signal transducer and activator of transcription (STAT) proteins are among the most well studied of the latent cytoplasmic signal-dependent transcription-factor pathways. In addition to several roles in normal cell decisions, dysregulation of STAT function contributes to human disease, making the study of these proteins an important topic of current research.
2,720 citations
TL;DR: This paper showed that the classical models of G-protein coupling and activation of second-messenger-generating enzymes do not fully explain seven-transmembrane receptors' remarkably diverse biological actions.
Abstract: Seven-transmembrane receptors, which constitute the largest, most ubiquitous and most versatile family of membrane receptors, are also the most common target of therapeutic drugs. Recent findings indicate that the classical models of G-protein coupling and activation of second-messenger-generating enzymes do not fully explain their remarkably diverse biological actions.
2,300 citations
TL;DR: In this review, the cellular roles of these enzymes are examined from a molecular point of view.
Abstract: DNA topoisomerases are the magicians of the DNA world — by allowing DNA strands or double helices to pass through each other, they can solve all of the topological problems of DNA in replication, transcription and other cellular transactions. Extensive biochemical and structural studies over the past three decades have provided molecular models of how the various subfamilies of DNA topoisomerase manipulate DNA. In this review, the cellular roles of these enzymes are examined from a molecular point of view.
2,194 citations
TL;DR: Advances include the continued development of 'passive' markers for the measurement of biomolecule expression and localization in live cells, and 'active' indicators for monitoring more complex cellular processes such as small-molecule-messenger dynamics, enzyme activation and protein–protein interactions.
Abstract: Fluorescent probes are one of the cornerstones of real-time imaging of live cells and a powerful tool for cell biologists. They provide high sensitivity and great versatility while minimally perturbing the cell under investigation. Genetically-encoded reporter constructs that are derived from fluorescent proteins are leading a revolution in the real-time visualization and tracking of various cellular events. Recent advances include the continued development of 'passive' markers for the measurement of biomolecule expression and localization in live cells, and 'active' indicators for monitoring more complex cellular processes such as small-molecule-messenger dynamics, enzyme activation and protein-protein interactions.
1,895 citations
TL;DR: The functional and structural properties of the IAP gene family, a group of structurally related proteins that, in addition to their ability to suppress apoptotic cell death, are involved in an increasing number of seemingly unrelated cellular functions, are reviewed.
Abstract: The 'inhibitor of apoptosis' (IAP) gene family, which was discovered less than a decade ago, encodes a group of structurally related proteins that, in addition to their ability to suppress apoptotic cell death, are involved in an increasing number of seemingly unrelated cellular functions. Here, we review the functional and structural properties of this fascinating group of proteins, and of several recently identified IAP-binding factors that regulate IAP function.
1,710 citations
TL;DR: The Snail superfamily of zinc-finger transcription factors is involved in processes that imply pronounced cell movements, both during embryonic development and in the acquisition of invasive and migratory properties during tumour progression.
Abstract: The Snail superfamily of zinc-finger transcription factors is involved in processes that imply pronounced cell movements, both during embryonic development and in the acquisition of invasive and migratory properties during tumour progression. Different family members have also been implicated in the signalling cascade that confers left–right identity, as well as in the formation of appendages, neural differentiation, cell division and cell survival.
1,660 citations
TL;DR: From sites of transcription in the nucleus to the outreaches of the cytoplasm, messenger RNAs are associated with RNA-binding proteins that communicate crucial information to the translation machinery for the surveillance of nonsense mutations and for mRNA localization and translation.
Abstract: From sites of transcription in the nucleus to the outreaches of the cytoplasm, messenger RNAs are associated with RNA-binding proteins. These proteins influence pre-mRNA processing as well as the transport, localization, translation and stability of mRNAs. Recent discoveries have shown that one group of these proteins marks exon exon junctions and has a role in mRNA export. These proteins communicate crucial information to the translation machinery for the surveillance of nonsense mutations and for mRNA localization and translation.
1,385 citations
TL;DR: The ezrin–radixin–moesin (ERM) proteins are crucial components that provide a regulated linkage between membrane proteins and the cortical cytoskeleton, and also participate in signal-transduction pathways.
Abstract: A fundamental property of many plasma-membrane proteins is their association with the underlying cytoskeleton to determine cell shape, and to participate in adhesion, motility and other plasma-membrane processes, including endocytosis and exocytosis. The ezrin–radixin–moesin (ERM) proteins are crucial components that provide a regulated linkage between membrane proteins and the cortical cytoskeleton, and also participate in signal-transduction pathways. The closely related tumour suppressor merlin shares many properties with ERM proteins, yet also provides a distinct and essential function.
1,347 citations
TL;DR: The sorting of proteins into the inner vesicles of multivesicular bodies is required for many key cellular processes, which range from the downregulation of activated signalling receptors to the proper stimulation of the immune response.
Abstract: The sorting of proteins into the inner vesicles of multivesicular bodies is required for many key cellular processes, which range from the downregulation of activated signalling receptors to the proper stimulation of the immune response. Recent advances in our understanding of the multivesicular-body sorting pathway have resulted from the identification of ubiquitin as a signal for the efficient sorting of proteins into this transport route, and from the discovery of components of the sorting and regulatory machinery that directs this complex process.
1,231 citations
TL;DR: The urokinase receptor uPAR was originally thought to assist the directional invasion of migrating cells, but it is now becoming increasingly evident that this proteinase receptor elicits a plethora of cellular responses that include cellular adhesion, differentiation, proliferation and migration in a non-proteolytic fashion.
Abstract: The plasminogen system has been implicated in clot lysis, wound healing, tissue regeneration, cancer and many other processes that affect health and disease. The urokinase receptor uPAR was originally thought to assist the directional invasion of migrating cells, but it is now becoming increasingly evident that this proteinase receptor elicits a plethora of cellular responses that include cellular adhesion, differentiation, proliferation and migration in a non-proteolytic fashion.
TL;DR: The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators as mentioned in this paper, and individual E2Fs can be divided into distinct subgroups that act in direct opposition to one another.
Abstract: The E2F transcription factor family determines whether or not a cell will divide by controlling the expression of key cell-cycle regulators. The individual E2Fs can be divided into distinct subgroups that act in direct opposition to one another to promote either cellular proliferation or cell-cycle exit and terminal differentiation. What is the underlying molecular basis of this 'push-me-pull-you' regulation, and what are its biological consequences?
TL;DR: The concept of bidirectional signalling has emerged as an important mechanism by which Ephs and ephrins control the output signal in processes of cell–cell communication.
Abstract: Eph receptors constitute the largest family of tyrosine kinase receptors and, together with their plasma-membrane-bound ephrin ligands, have many important functions during development and adulthood. In contrast with most receptor tyrosine kinases, unidirectional signalling can originate from the ephrin ligands as well as from the Eph receptors. Furthermore, the concept of bidirectional signalling has emerged as an important mechanism by which Ephs and ephrins control the output signal in processes of cell–cell communication.
TL;DR: The pH of intracellular compartments in eukaryotic cells is a carefully controlled parameter that affects many cellular processes, including intrACEllular membrane transport, prohormone processing and transport of neurotransmitters, as well as the entry of many viruses into cells.
Abstract: The pH of intracellular compartments in eukaryotic cells is a carefully controlled parameter that affects many cellular processes, including intracellular membrane transport, prohormone processing and transport of neurotransmitters, as well as the entry of many viruses into cells. The transporters responsible for controlling this crucial parameter in many intracellular compartments are the vacuolar (H+)-ATPases (V-ATPases). Recent advances in our understanding of the structure and regulation of the V-ATPases, together with the mapping of human genetic defects to genes that encode V-ATPase subunits, have led to tremendous excitement in this field.
TL;DR: In muscle and fat cells, insulin stimulates the delivery of the glucose transporter GLUT4 from an intracellular location to the cell surface, where it facilitates the reduction of plasma glucose levels.
Abstract: In muscle and fat cells, insulin stimulates the delivery of the glucose transporter GLUT4 from an intracellular location to the cell surface, where it facilitates the reduction of plasma glucose levels. Understanding the molecular mechanisms that mediate this translocation event involves integrating our knowledge of two fundamental processes--the signal transduction pathways that are triggered when insulin binds to its receptor and the membrane transport events that need to be modified to divert GLUT4 from intracellular storage to an active plasma membrane shuttle service.
TL;DR: This review summarizes various features of furin — its structural and enzymatic properties, intracellular localization, trafficking, substrates, and roles in vivo.
Abstract: Furin catalyses a simple biochemical reaction--the proteolytic maturation of proprotein substrates in the secretory pathway. But the simplicity of this reaction belies furin's broad and important roles in homeostasis, as well as in diseases ranging from Alzheimer's disease and cancer to anthrax and Ebola fever. This review summarizes various features of furin--its structural and enzymatic properties, intracellular localization, trafficking, substrates, and roles in vivo.
TL;DR: It is 40 years since the first member of what came to be known as the matrix metalloproteinase (MMP) family was described and structural, molecular and biochemical approaches have subsequently contributed to piecing together the puzzle of how MMPs work, and how they contribute to various disease processes.
Abstract: It is 40 years since the first member of what came to be known as the matrix metalloproteinase (MMP) family was described. Structural, molecular and biochemical approaches have subsequently contributed to piecing together the puzzle of how MMPs work, and how they contribute to various disease processes.
TL;DR: The Mre 11 complex is a multisubunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2 and its functions in checkpoint signalling and DNA replication are uncovered.
Abstract: The Mre11 complex is a multisubunit nuclease that is composed of Mre11, Rad50 and Nbs1/Xrs2. Mutations in the genes that encode components of this complex result in DNA- damage sensitivity, genomic instability, telomere shortening and aberrant meiosis. The molecular defect that underlies these phenotypes has long been thought to be related to a DNA repair deficiency. However, recent studies have uncovered functions for the Mre11 complex in checkpoint signalling and DNA replication.
TL;DR: Bacterial cell-to-cell signalling has emerged as a new area in microbiology where individual bacterial cells communicate with each other and co-ordinate group activities.
Abstract: Bacterial cell-to-cell signalling has emerged as a new area in microbiology. Individual bacterial cells communicate with each other and co-ordinate group activities. Although a lot of detail is known about the mechanisms of a few well-characterized bacterial communication systems, other systems have been discovered only recently. Bacterial intercellular communication has become a target for the development of new anti-virulence drugs.
TL;DR: Recent studies of protein tyrosine kinases and G-protein-coupled receptors have shed new light on the mechanisms and functional consequences of this bidirectional interplay between signalling and membrane-transport networks.
Abstract: Binding of hormones, growth factors and other cell modulators to cell-surface receptors triggers a complex array of signal-transduction events. The activation of many receptors also accelerates their endocytosis. Endocytic transport is important in regulating signal transduction and in mediating the formation of specialized signalling complexes. Conversely, signal-transduction events modulate specific components of the endocytic machinery. Recent studies of protein tyrosine kinases and G-protein-coupled receptors have shed new light on the mechanisms and functional consequences of this bidirectional interplay between signalling and membrane-transport networks.
TL;DR: Research into second messengers has provided a framework for understanding transmembrane signal transduction, receptor–effector coupling, protein-kinase cascades and downregulation of drug responsiveness.
Abstract: Since the discovery in 1957 that cyclic AMP acts as a second messenger for the hormone adrenaline, interest in this molecule and its companion, cyclic GMP, has grown Over a period of nearly 50 years, research into second messengers has provided a framework for understanding transmembrane signal transduction, receptor-effector coupling, protein-kinase cascades and downregulation of drug responsiveness The breadth and impact of this work is reflected by five different Nobel prizes
TL;DR: The Notch signalling pathway uses a relatively direct mechanism, in which the intracellular domain of the receptor is liberated by intramembrane cleavage and translocates to the nucleus as discussed by the authors.
Abstract: Many cell-surface receptors transmit signals to the nucleus through complex protein cascades. By contrast, the Notch signalling pathway uses a relatively direct mechanism, in which the intracellular domain of the receptor is liberated by intramembrane cleavage and translocates to the nucleus. This critical cleavage is mediated by the gamma-secretase complex, and new findings reveal that this mechanism is used by various receptors, although many questions remain about the biochemical details.
TL;DR: The ability to take up substances from the surrounding environment not only provides cells with vital nutrients, but also enables the selective transport of substances from one compartment to another.
Abstract: The ability to take up substances from the surrounding environment not only provides cells with vital nutrients, but also enables the selective transport of substances from one compartment to another. Megalin and cubilin are two structurally different endocytic receptors that interact to serve such functions. Evidence has accumulated in recent years to indicate that these receptors have important functions in both normal physiology and pathology.
TL;DR: Findings indicating that NO might function not only as a physiological regulator of cell respiration, but also to augment the generation of reactive oxygen species by mitochondria, and thereby trigger mechanisms of cell survival or death are reviewed.
Abstract: The physiological role of nitric oxide (NO) in the maintenance of vascular tone, in synaptic transmission and in cellular defence is now firmly established. Recent evidence indicates that NO can also affect mitochondrial function. Here, we review findings indicating that NO — through its interaction with components of the electron-transport chain — might function not only as a physiological regulator of cell respiration, but also to augment the generation of reactive oxygen species by mitochondria, and thereby trigger mechanisms of cell survival or death.
TL;DR: In this paper, a review of emerging degradomic techniques and concepts for protease and protease-substrate repertoires identification is presented, which will facilitate the identification of new pharmaceutical targets to treat disease.
Abstract: Degradomics — the application of genomic and proteomic approaches to identify the protease and protease-substrate repertoires, or 'degradomes', on an organism-wide scale — promises to uncover new roles for proteases in vivo. This knowledge will facilitate the identification of new pharmaceutical targets to treat disease. Here, we review emerging degradomic techniques and concepts.
TL;DR: The recent identification of new redox-active proteins in humans and yeast that mechanistically parallel the more established redox -active enzymes indicates that there might be further uncharacterized redox pathways throughout the cell.
Abstract: Protein disulphide bonds are formed in the endoplasmic reticulum of eukaryotic cells and the periplasmic space of prokaryotic cells The main pathways that catalyse the formation of protein disulphide bonds in prokaryotes and eukaryotes are remarkably similar, and they share several mechanistic features The recent identification of new redox-active proteins in humans and yeast that mechanistically parallel the more established redox-active enzymes indicates that there might be further uncharacterized redox pathways throughout the cell
TL;DR: The phytochrome molecule must relay this information to nuclear genes that are poised to respond by directing appropriate adjustments in growth and development, through the intricate intracellular signalling networks through which this sensory information is transduced.
Abstract: Light is life for plants. To continuously assess and adapt to fluctuations in the quality and quantity of this essential commodity, plants deploy sensory photoreceptors, including the phytochromes. Having captured an incoming photon, the activated phytochrome molecule must relay this information to nuclear genes that are poised to respond by directing appropriate adjustments in growth and development. Defining the intricate intracellular signalling networks through which this sensory information is transduced is an area of intense research activity.
TL;DR: The mechanism of retro-translocation is still mysterious, but several aspects of this process are now being unravelled.
Abstract: Proteins that are misfolded in the endoplasmic reticulum are transported back into the cytosol for destruction by the proteasome. This retro-translocation pathway has been co-opted by certain viruses, and by plant and bacterial toxins. The mechanism of retro-translocation is still mysterious, but several aspects of this process are now being unravelled.
TL;DR: Eukaryotic cells coordinate protein-folding reactions in the endoplasmic reticulum with gene expression in the nucleus and messenger RNA translation in the cytoplasm to regulate cell differentiation to survive nutrient-limiting conditions or to produce large amounts of secreted products.
Abstract: Eukaryotic cells coordinate protein-folding reactions in the endoplasmic reticulum with gene expression in the nucleus and messenger RNA translation in the cytoplasm. As the rate of protein synthesis increases, protein folding can be compromised, so cells have evolved signal-transduction pathways that control transcription and translation -- the 'unfolded protein response'. Recent studies indicate that these pathways also coordinate rates of protein synthesis with nutrient and energy stores, and regulate cell differentiation to survive nutrient-limiting conditions or to produce large amounts of secreted products such as hormones, antibodies or growth factors.
TL;DR: It is proposed that the morphogenetic behaviour of epithelial cells is guided by two distinct elements: an intrinsic differentiation programme that drives formation of a lumen-enclosing monolayer, and a growth factor-induced, transient de-differentiation that allows this monolayers to be remodelled.
Abstract: How do individual cells organize into multicellular tissues? Here, we propose that the morphogenetic behaviour of epithelial cells is guided by two distinct elements: an intrinsic differentiation programme that drives formation of a lumen-enclosing monolayer, and a growth factor-induced, transient de-differentiation that allows this monolayer to be remodelled.