Abstract：
:The notion of feedback is fundamental for understanding signal transduction networks. Feedback loops attenuate or amplify signals, change the network dynamics and modify the input-output relationships between the signal and the target. Negative feedback provides robustness to noise and adaptation to perturbations, but as a double-edged sword can prevent effective pathway inhibition by a drug. Positive feedback brings about switch-like network responses and can convert analog input signals into digital outputs, triggering cell fate decisions and phenotypic changes. We show how a multitude of protein-protein interactions creates hidden feedback loops in signal transduction cascades. Drug treatments that interfere with feedback regulation can cause unexpected adverse effects. Combinatorial molecular interactions generated by pathway crosstalk and feedback loops often bypass the block caused by targeted therapies against oncogenic mutated kinases. We discuss mechanisms of drug resistance caused by network adaptations and suggest that development of effective drug combinations requires understanding of how feedback loops modulate drug responses.
journal_name
Semin Cell Dev Bioljournal_title
Seminars in cell & developmental biologyauthors
Nguyen LK,Kholodenko BNdoi
10.1016/j.semcdb.2015.09.024subject
Has Abstractpub_date
2016-02-01 00:00:00pages
85-94eissn
1084-9521issn
1096-3634pii
S1084-9521(15)00184-6journal_volume
50pub_type
杂志文章,评审abstract：:The localisation of transcripts to specific regions of the cell probably occurs in all cell types and has many distinct functions that go from the control of body axis formation to learning and memory. mRNAs can be localised by a variety of mechanisms including local protection from degradation, diffusion to a localis...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2007.01.008
更新日期：2007-04-01 00:00:00
abstract：:Pollen tubes extend rapidly in an oscillatory manner by the extreme form of polarized growth, tip growth, and provide an exciting system for studying the spatiotemporal control of polarized cell growth. The Rho-family ROP GTPase is a key signaling molecule in this growth control and is periodically activated at the ap...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2011.06.004
更新日期：2011-10-01 00:00:00
abstract：:Vascular plants, unlike bryophytes, have a strong root-shoot dichotomy in which the tissue systems are mutually interdependent; roots are completely dependent on shoots for photosynthetic sugars, and shoots are completely dependent on roots for water and mineral nutrients. Long-distance communication between shoot and...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2020.06.011
更新日期：2020-06-20 00:00:00
abstract：:Most mammals cannot easily overcome degenerative disease or traumatic injuries. In contrast, an innate ability to regenerate is observed across animal phyla. Freshwater planarians are amongst the organisms that are capable of stem cell-mediated whole-body regeneration and have served as an exemplary model to study how...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2018.04.009
更新日期：2019-03-01 00:00:00
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2014.06.018
更新日期：2014-11-01 00:00:00
abstract：:Rheumatoid arthritis (RA) is a prevalent inflammatory joint disease with enigmatic flares, which causes swelling, pain, and irreversible connective tissue damage. Recently, it has been demonstrated in murine models of RA that the popliteal lymph node (PLN) is a biomarker of arthritic flare, as it "expands" in size and...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2015.01.001
更新日期：2015-02-01 00:00:00
abstract：:In eukaryotic cells, the membranes of different intracellular organelles have different lipid composition, and various biomembranes show an asymmetric distribution of lipid types across the membrane bilayer. Membrane lipid organization reflects a dynamic equilibrium of lipids moving across the bilayer in both directio...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1006/scdb.2000.0231
更新日期：2001-04-01 00:00:00
abstract：:Stem cells have become one of the "buzz" topics in the last decade or so. One of the best systems to study adult stem cells in vivo is in the model organism, Drosophila melanogaster. One hundred years of genetic analysis, a sequenced and highly annotated genome and genomics makes this a difficult organism to avoid. Th...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2008.06.003
更新日期：2008-08-01 00:00:00
abstract：:In recent years, novel functions for a number of nuclear factors have been uncovered in the cytoplasm, mainly at the level of translation. These factors behave as multifunctional regulators of gene expression and many play key roles in cell differentiation and development. One of the best characterized examples is tha...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章
doi：10.1006/scdb.1997.0181
更新日期：1997-12-01 00:00:00
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2005.03.004
更新日期：2005-08-01 00:00:00
abstract：:How limited is the ability of stem cells to generate gametes or differentiated somatic cells? Recent outcomes of research with stem cells from both embryonic and adult origin will be discussed with particular attention to results that challenge conventional wisdom about the presence of reproductive stem cells in adult...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2006.07.003
更新日期：2006-08-01 00:00:00
abstract：:With the arrival of atomic force microscopy (AFM) about thirty years ago, this new imaging tool opened up a new area for the exploration of biological samples, ranging from the tissue and cellular level down to the supramolecular scale. Commercial instruments of this new imaging technique began to appear in the five y...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2017.07.001
更新日期：2018-01-01 00:00:00
abstract：:Cellular morphogenesis is a complex process and molecular studies in the last few decades have amassed a large amount of information that is difficult to grasp in any completeness. Fungal systems, in particular the budding and fission yeasts, have been important players in unravelling the basic structural and regulato...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2008.01.003
更新日期：2008-06-01 00:00:00
abstract：:When entering tissues, monocytes can differentiate into cells that share morphological and functional features with either dendritic cells (DC) or macrophages. Monocyte-derived DC have been observed in humans at mucosal tissues and in inflammatory settings, where they are usually referred to as «inflammatory DC». In t...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2018.02.018
更新日期：2019-02-01 00:00:00
abstract：:There has been widespread speculation regarding the possibility of reprogramming human somatic nuclei by transfer into oocytes. Stem cells derived from such reconstructed embryos could theoretically provide a source of autologous tissue for therapeutic transplantation. However the biological, technical and ethical hur...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1006/scdb.1999.0277
更新日期：1999-06-01 00:00:00
abstract：:Eukaryotic cells have a highly evolved system of protein secretion, and dysfunction in this pathway is associated with many diseases including cancer, infection, metabolic disease and neurological disorders. Most proteins are secreted using the conventional endoplasmic reticulum (ER)/Golgi network and as such, this pa...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2018.02.022
更新日期：2018-11-01 00:00:00
abstract：:MicroRNAs (miRNAs) have emerged as an essential regulatory component in plants. Many of the known miRNAs are evolutionarily conserved across diverse plant species and function in the regulatory control of fundamentally important biological processes such as developmental timing, patterning, and response to environment...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2010.03.012
更新日期：2010-10-01 00:00:00
abstract：:Two neurotrophins and their two receptors appear to regulate the survival of vestibular and cochlear neurons in the developing ear. Mice lacking either brain derived neurotrophic factor (BDNF) or its associated receptor, Trk B, show a severe reduction in the number of vestibular neurons and a loss of all innervation t...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章
doi：10.1006/scdb.1997.0144
更新日期：1997-06-01 00:00:00
abstract：:The Notch pathway is one of the major signaling pathways required for proper development in metazoans. Notch activity is regulated at numerous levels, and increasing evidence reveals the importance of "protein glycosylation" (modification of Notch receptors with sugars) for its regulation. In this review we summarize ...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2010.03.003
更新日期：2010-08-01 00:00:00
abstract：:During development, diffusible ligands, known as morphogens, are thought to move across fields of cells, regulating gene expression in a concentration dependent manner. The case for morphogens has been convincingly made for the Decapentapleigic (Dpp), Wingless (Wg) and Hedgehog (Hh) proteins in the Drosophila wing. In...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/s1084-9521(02)00014-9
更新日期：2002-04-01 00:00:00
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journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章
doi：10.1006/scdb.1997.0165
更新日期：1997-08-01 00:00:00
abstract：:Asymmetric division is a fundamental mechanism of generating cell diversity during development. One of its hallmarks is asymmetric localization during mitosis of proteins that specify daughter cell fate. Studies in Drosophila show that subcellular localization of many proteins required for asymmetric division of neuro...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2005.02.005
更新日期：2005-06-01 00:00:00
abstract：:Spectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which ar...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2017.05.019
更新日期：2017-09-01 00:00:00
abstract：:Extracellular vesicles (EVs), lipid bilayer-enclosed structures that contain a variety of biological molecules shed by cells, are increasingly becoming appreciated as a major form of cell-to-cell communication. Indeed, EVs have been shown to play important roles in several physiological processes, as well as diseases ...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2017.01.002
更新日期：2017-07-01 00:00:00
abstract：:Viruses have evolved strategies to evade immunity mediated by antibody and complement. Herpesviruses and coronaviruses encode IgG Fc binding proteins that inhibit IgG activity, enabling the virus or infected cell to escape antibody attack. Herpesviruses, vaccinia virus and HIV-1 have the capacity to interfere with com...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1006/scdb.1998.0242
更新日期：1998-06-01 00:00:00
abstract：:Research using Xenopus laevis has made enormous contributions to our understanding of vertebrate development, control of the eukaryotic cell cycle and the cytoskeleton. One limitation, however, has been the lack of systematic genetic studies in Xenopus to complement molecular and cell biological investigations. Work w...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2005.11.009
更新日期：2006-02-01 00:00:00
abstract：:Cell motility is a tightly regulated process that involves the polymerization of actin subunits. The formation of actin filaments is controlled through a variety of protein factors that accelerate or perturb the polymerization process. As is the case for most biological events, cell movement is also controlled at the ...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2014.05.012
更新日期：2014-10-01 00:00:00
abstract：:Anuran amphibians can regenerate the retina through differentiation of stem cells in the ciliary marginal zone and through transdifferentiation of the retinal pigmented epithelium. By contrast, the regeneration of the lens has been demonstrated only in larvae of species belonging to the Xenopus genus, where the lens r...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2008.11.015
更新日期：2009-07-01 00:00:00
abstract：:Traumatic brain injury (TBI) is a neurological condition which affects a large number of individuals worldwide, across all ages. It can lead to major physical, cognitive and psychological impairment, and represents a considerable health cost burden. TBI is a heterogeneous condition and there has been intense effort ov...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2020.08.004
更新日期：2020-10-06 00:00:00
abstract：:Control of translation allows for the production of stoichiometric levels of each protein in the cell. Attaining such a level of fine-tuned regulation of protein production requires the coordinated temporal and spatial control of numerous cellular signalling cascades impinging on the various components of the translat...
journal_title：Seminars in cell & developmental biology
pub_type： 杂志文章,评审
doi：10.1016/j.semcdb.2014.09.014
更新日期：2014-12-01 00:00:00
