The Experts below are selected from a list of 32999922 Experts worldwide ranked by ideXlab platform
Toru Takumi - One of the best experts on this subject based on the ideXlab platform.
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A direct repeat of E-Box-like elements is required for cell-autonomous circadian rhythm of clock genes
BMC Molecular Biology, 2008Co-Authors: Yasukazu Nakahata, Mayumi Yoshida, Atsuko Takano, Haruhiko Soma, Takuro Yamamoto, Akio Yasuda, Toru Nakatsu, Toru TakumiAbstract:Background The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-Box (CACGTG). The non-canonical E-Boxes or E-Box-like sequences have also been reported to be necessary for circadian oscillation. Results We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-Box or a non-canonical E-Box and an E-Box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-Box or E-Box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-Box-like elements in their promoter region. Conclusion We propose a novel possible mechanism regulated by double E-Box-like elements, not to a single E-Box, for circadian transcriptional oscillation. The direct repeat of the E-Box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes.
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A direct repeat of E-Box-like elements is required for cell-autonomous circadian rhythm of clock genes
BMC molecular biology, 2008Co-Authors: Yasukazu Nakahata, Mayumi Yoshida, Atsuko Takano, Haruhiko Soma, Takuro Yamamoto, Akio Yasuda, Toru Nakatsu, Toru TakumiAbstract:The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-Box (CACGTG). The non-canonical E-Boxes or E-Box-like sequences have also been reported to be necessary for circadian oscillation. We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-Box or a non-canonical E-Box and an E-Box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-Box or E-Box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-Box-like elements in their promoter region. We propose a novel possible mechanism regulated by double E-Box-like elements, not to a single E-Box, for circadian transcriptional oscillation. The direct repeat of the E-Box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes.
Johannes Lengler - One of the best experts on this subject based on the ideXlab platform.
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introducing elitist black box models when does elitist behavior weaken the performance of evolutionary algorithms
Evolutionary Computation, 2016Co-Authors: Carola Doerr, Johannes LenglerAbstract:Black-box complexity theory provides lower bounds for the runtime of black-box optimizers like evolutionary algorithms and other search heuristics and serves as an inspiration for the design of new genetic algorithms. Several black-box models covering different classes of algorithms exist, each highlighting a different aspect of the algorithms under considerations. In this work we add to the existing black-box notions a new elitist black-box model, in which algorithms are required to base all decisions solely on (the relative performance of) a fixed number of the best search points sampled so far. Our elitist model thus combines features of the ranking-based and the memory-restricted black-box models with an enforced usage of truncation selection. We provide several examples for which the elitist black-box complexity is exponentially larger than that of the respective complexities in all previous black-box models, thus showing that the elitist black-box complexity can be much closer to the runtime of typi...
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Elitist Black-Box Models: Analyzing the Impact of Elitist Selection on the Performance of Evolutionary Algorithms
2015Co-Authors: Carola Doerr, Johannes LenglerAbstract:Black-box complexity theory provides lower bounds for the runtime %classes of black-box optimizers like evolutionary algorithms and serves as an inspiration for the design of new genetic algorithms. Several black-box models covering different classes of algorithms exist, each highlighting a different aspect of the algorithms under considerations. In this work we add to the existing black-box notions a new \emph{elitist black-box model}, in which algorithms are required to base all decisions solely on (a fixed number of) the best search points sampled so far. Our model combines features of the ranking-based and the memory-restricted black-box models with elitist selection. We provide several examples for which the elitist black-box complexity is exponentially larger than that the respective complexities in all previous black-box models, thus showing that the elitist black-box complexity can be much closer to the runtime of typical evolutionary algorithms. We also introduce the concept of $p$-Monte Carlo black-box complexity, which measures the time it takes to optimize a problem with failure probability at most p. Even for small $p$, the $p$-Monte Carlo black-box complexity of a function class F can be smaller by an exponential factor than its typically regarded Las Vegas complexity (which measures the expected time it takes to optimize F).
Xing Wang Deng - One of the best experts on this subject based on the ideXlab platform.
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b box containing proteins bbx30 and bbx31 acting downstream of hy5 negatively regulate photomorphogenesis in arabidopsis
Plant Physiology, 2019Co-Authors: Dongqing Xu, Yan Jiang, Xing Wang Deng, Yueqin Heng, Mingquan Ding, Hua Zhou, Xianhai ZhaoAbstract:Light-mediated seedling development is coordinately controlled by a variety of key regulators. Here, we identified two B-box (BBX)-containing proteins, BBX30 and BBX31, as repressors of photomorphogenesis. ELONGATED HYPOCOTYL5, a central regulator of light signaling, directly binds to the G-box cis-element present in the promoters of BBX30 and BBX31 and negatively controls their transcription levels in the light. Seedlings with mutations in BBX30 or BBX31 are hypersensitive to light, whereas the overexpression of BBX30 or BBX31 leads to hypo-photomorphogenic growth in the light. Furthermore, transgenic and phenotypic analysis revealed that the B-box domain of BBX30 or BBX31 is essential for their respective functioning in the regulation of photomorphogenic development in plants. In conclusion, BBX30 and BBX31 act as key negative regulators of light signaling, and their transcription is repressed by ELONGATED HYPOCOTYL5 through directly associating with their promoters.
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the b box domain protein bbx21 promotes photomorphogenesis
Plant Physiology, 2017Co-Authors: Dongqing Xu, Yan Jiang, Jian Li, Magnus Holm, Xing Wang DengAbstract:B-box-containing (BBX) proteins play critical roles in a variety of cellular and developmental processes in plants. BBX21 (also known as SALT TOLERANCE HOMOLOG2), which contains two B-box domains in tandem at the N terminus, has been previously demonstrated as a key component involved in the COP1-HY5 signaling hub. However, the exact molecular and physiological roles of B-box domains in BBX21 are largely unclear. Here, we found that structurally disruption of the second B-box domain, but not the first one, in BBX21 completely abolishes its biological and physiological activity in conferring hyperphotomorphogenetic phenotype in Arabidopsis (Arabidopsis thaliana). Intact B-box domains in BBX21 are not required for interaction with COP1 and its degradation by COP1 via the 26S proteasome system. However, disruption of the second B-box of BBX21 nearly impairs its ability for binding of T/G-box within the HY5 promoter both in vitro and in vivo, as well as controlling HY5 and HY5-regulated gene expression in Arabidopsis seedlings. Taken together, this study provides a mechanistic framework in which BBX21 directly binds to the T/G-box present in the HY5 promoter possibly through its second B-box domain, which in turn controls HY5 and HY5-regulated gene expression to promote photomorphogenesis.
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bbx21 an arabidopsis b box protein directly activates hy5 and is targeted by cop1 for 26s proteasome mediated degradation
Proceedings of the National Academy of Sciences of the United States of America, 2016Co-Authors: Yan Jiang, Magnus Holm, Fang Lin, Xing Wang DengAbstract:BBX21 (also known as SALT TOLERANCE HOMOLOG 2), a B-box (BBX)-containing protein, has been previously identified as a positive regulator of light signaling; however, the precise role of BBX21 in regulating seedling photomorphogenesis remains largely unclear. In this study, we report that CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) interacts with BBX21 in vivo and is able to ubiquitinate BBX21 in vitro. Thus, BBX21 is targeted for 26S proteasome-mediated degradation in dark-grown Arabidopsis seedlings in a COP1-dependent manner. Moreover, we show that BBX21 binds to the T/G-box in the ELONGATED HYPOCOTYL 5 (HY5) promoter and directly activates HY5 expression in the light. Transgenic seedlings overexpressing BBX21 exhibit dramatically shortened hypocotyls in the light, and this phenotype is dependent on a functional HY5. Taken together, our data suggest a molecular base underlying BBX21-mediated seedling photomorphogenesis, indicating that BBX21 is a pivotal component involved in the COP1-HY5 regulatory hub.
Yasukazu Nakahata - One of the best experts on this subject based on the ideXlab platform.
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A direct repeat of E-Box-like elements is required for cell-autonomous circadian rhythm of clock genes
BMC Molecular Biology, 2008Co-Authors: Yasukazu Nakahata, Mayumi Yoshida, Atsuko Takano, Haruhiko Soma, Takuro Yamamoto, Akio Yasuda, Toru Nakatsu, Toru TakumiAbstract:Background The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-Box (CACGTG). The non-canonical E-Boxes or E-Box-like sequences have also been reported to be necessary for circadian oscillation. Results We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-Box or a non-canonical E-Box and an E-Box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-Box or E-Box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-Box-like elements in their promoter region. Conclusion We propose a novel possible mechanism regulated by double E-Box-like elements, not to a single E-Box, for circadian transcriptional oscillation. The direct repeat of the E-Box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes.
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A direct repeat of E-Box-like elements is required for cell-autonomous circadian rhythm of clock genes
BMC molecular biology, 2008Co-Authors: Yasukazu Nakahata, Mayumi Yoshida, Atsuko Takano, Haruhiko Soma, Takuro Yamamoto, Akio Yasuda, Toru Nakatsu, Toru TakumiAbstract:The circadian expression of the mammalian clock genes is based on transcriptional feedback loops. Two basic helix-loop-helix (bHLH) PAS (for Period-Arnt-Sim) domain-containing transcriptional activators, CLOCK and BMAL1, are known to regulate gene expression by interacting with a promoter element termed the E-Box (CACGTG). The non-canonical E-Boxes or E-Box-like sequences have also been reported to be necessary for circadian oscillation. We report a new cis-element required for cell-autonomous circadian transcription of clock genes. This new element consists of a canonical E-Box or a non-canonical E-Box and an E-Box-like sequence in tandem with the latter with a short interval, 6 base pairs, between them. We demonstrate that both E-Box or E-Box-like sequences are needed to generate cell-autonomous oscillation. We also verify that the spacing nucleotides with constant length between these 2 E-elements are crucial for robust oscillation. Furthermore, by in silico analysis we conclude that several clock and clock-controlled genes possess a direct repeat of the E-Box-like elements in their promoter region. We propose a novel possible mechanism regulated by double E-Box-like elements, not to a single E-Box, for circadian transcriptional oscillation. The direct repeat of the E-Box-like elements identified in this study is the minimal required element for the generation of cell-autonomous transcriptional oscillation of clock and clock-controlled genes.
Michele Pagano - One of the best experts on this subject based on the ideXlab platform.
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Mechanisms and function of substrate recruitment by F-box proteins
Nature Reviews Molecular Cell Biology, 2013Co-Authors: Jeffrey R. Skaar, Julia K. Pagan, Michele PaganoAbstract:S phase kinase-associated protein 1 (SKP1)–cullin 1 (CUL1)–F-box protein (SCF) ubiquitin ligase complexes use a family of F-box proteins as substrate adaptors to mediate the degradation of a large number of regulatory proteins involved in diverse processes. The dysregulation of SCF complexes and their substrates contributes to multiple pathologies. In the 14 years since the identification and annotation of the F-box protein family, the continued identification and characterization of novel substrates has greatly expanded our knowledge of the regulation of substrate targeting and the roles of F-box proteins in biological processes. Here, we focus on the evolution of our understanding of substrate recruitment by F-box proteins, the dysregulation of substrate recruitment in disease and potential avenues for F-box protein-directed disease therapies. F-box proteins are the substrate-targeting subunits of S phase kinase-associated protein 1 (SKP1)–cullin 1 (CUL1)–F-box protein (SCF) ubiquitin ligase complexes. In mammals, approximately 70 F-box proteins, each able to target multiple substrates, enable SCF complexes to control the levels of many regulatory proteins with diverse functions. F-box protein substrates are recognized through degradation motifs (degrons). The best-characterized F-box proteins recognize conserved consensus degron sequences that include phosphorylated amino acids (phosphodegrons). Although phosphodegrons remain the most common mechanism of substrate recognition by F-box proteins, many additional degron recognition mechanisms, both dependent on or independent of post-translational modifications, can facilitate substrate targeting. Because an individual F-box protein can regulate the degradation of multiple substrates, it can control multiple different pathways in response to various different stimuli. Therefore, F-box proteins can have context-dependent functions, including functions that may seem contradictory. The activity of F-box proteins can also be controlled directly through several mechanisms, including localization, expression and degradation. F-box proteins have key roles in cell regulatory mechanisms, and they are frequently dysregulated in diseases. Historically, the F-box protein family has been examined in the context of cancer, but these proteins have emerging roles in a wide range of other diseases. Through their role as substrate adaptors for S phase kinase-associated protein 1 (SKP1)–cullin 1 (CUL1)–F-box protein (SCF) ubiquitin ligase complexes, F-box proteins control the degradation of a large number of proteins with wide-ranging functions. Studying the mechanisms of substrate recruitment by F-box proteins has increased our understanding of their dysregulation in disease and might lead to targeted therapies.
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insights into scf ubiquitin ligases from the structure of the skp1 skp2 complex
Nature, 2000Co-Authors: Brenda A Schulman, Michele Pagano, Wade J Harper, Stephen J Elledge, Andrea C Carrano, Philip D Jeffrey, Zachary Bowen, E Kinnucan, Michael S Finnin, Nikola P PavletichAbstract:F-box proteins are members of a large family that regulates the cell cycle, the immune response, signalling cascades and developmental programmes by targeting proteins, such as cyclins, cyclin-dependent kinase inhibitors, IκBα and β-catenin, for ubiquitination (reviewed in refs 1,2,3). F-box proteins are the substrate-recognition components of SCF (Skp1–Cullin–F-box protein) ubiquitin-protein ligases4,5. They bind the SCF constant catalytic core by means of the F-box motif interacting with Skp1, and they bind substrates through their variable protein–protein interaction domains6. The large number of F-box proteins is thought to allow ubiquitination of numerous, diverse substrates6. Most organisms have several Skp1 family members, but the function of these Skp1 homologues and the rules of recognition between different F-box and Skp1 proteins remain unknown. Here we describe the crystal structure of the human F-box protein Skp2 bound to Skp1. Skp1 recruits the F-box protein through a bipartite interface involving both the F-box and the substrate-recognition domain. The structure raises the possibility that different Skp1 family members evolved to function with different subsets of F-box proteins, and suggests that the F-box protein may not only recruit substrate, but may also position it optimally for the ubiquitination reaction.
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the f box protein family
Genome Biology, 2000Co-Authors: Edward T Kipreos, Michele PaganoAbstract:The F-box is a protein motif of approximately 50 amino acids that functions as a site of protein-protein interaction. F-box proteins were first characterized as components of SCF ubiquitin-ligase complexes (named after their main components, Skp I, Cullin, and an F-box protein), in which they bind substrates for ubiquitin-mediated proteolysis. The F-box motif links the F-box protein to other components of the SCF complex by binding the core SCF component Skp I. F-box proteins have more recently been discovered to function in non-SCF protein complexes in a variety of cellular functions. There are 11 F-box proteins in budding yeast, 326 predicted in Caenorhabditis elegans, 22 in Drosophila, and at least 38 in humans. F-box proteins often include additional carboxy-terminal motifs capable of protein-protein interaction; the most common secondary motifs in yeast and human F-box proteins are WD repeats and leucine-rich repeats, both of which have been found to bind phosphorylated substrates to the SCF complex. The majority of F-box proteins have other associated motifs, and the functions of most of these proteins have not yet been defined.
