Pub Date : 2003-04-29DOI: 10.1126/scisignal.1802003tw165
Energy consumption and fat metabolism are the keys to controlling weight gain. Peroxisome proliferator-activated receptors (PPARs) are essential regulators of lipid storage and metabolism. The three isoforms of PPARs--PPARα, PPARγ, PPARδ--exhibit tissue-specific expression and functions. PPARγ stimulates adipogenesis and lipid storage, whereas PPARα stimulates lipid combustion in the liver. The role of PPARδ had not been determined. Wang et al. used transgenic mice overexpressing PPARδ in adipose tissue to show that PPARδ inhibited weight gain and blocked fat storage. In adipose tissue from the transgenic mice, PPARδ promoted expression of β oxidation enzymes, triglyceride hydrolysis enzymes involved in lipid metabolism, and of proteins that uncouple mitochondria, which allows cellular energy stores to be converted to heat (thermogenesis). In cultured cells overexpressing PPARδ, β-oxidation and triglyceride metabolism were increased in response to a PPARδ agonist. The effects of PPARδ were very similar to those of the transcriptional coactivator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) and in cultured cells or gastrocnemius muscle. PPARδ and PGC-1α coprecipitated, which suggested that the thermogenic effects of PGC-1α may be mediated through interaction with PPARδ. PPARδ agonists may provide yet another target in the war against obesity. Y.-X. Wang, C.-H. Lee, S. Tiep, R. T. Yu, J. Ham, H. Kang, R. M. Evans, Peroxisome-proliferator-activated receptor δ activates fat metabolism to prevent obesity. Cell 113, 159-170 (2003). [Online Journal]
{"title":"PPARδ: Burning off the Fat","authors":"","doi":"10.1126/scisignal.1802003tw165","DOIUrl":"https://doi.org/10.1126/scisignal.1802003tw165","url":null,"abstract":"Energy consumption and fat metabolism are the keys to controlling weight gain. Peroxisome proliferator-activated receptors (PPARs) are essential regulators of lipid storage and metabolism. The three isoforms of PPARs--PPARα, PPARγ, PPARδ--exhibit tissue-specific expression and functions. PPARγ stimulates adipogenesis and lipid storage, whereas PPARα stimulates lipid combustion in the liver. The role of PPARδ had not been determined. Wang et al. used transgenic mice overexpressing PPARδ in adipose tissue to show that PPARδ inhibited weight gain and blocked fat storage. In adipose tissue from the transgenic mice, PPARδ promoted expression of β oxidation enzymes, triglyceride hydrolysis enzymes involved in lipid metabolism, and of proteins that uncouple mitochondria, which allows cellular energy stores to be converted to heat (thermogenesis). In cultured cells overexpressing PPARδ, β-oxidation and triglyceride metabolism were increased in response to a PPARδ agonist. The effects of PPARδ were very similar to those of the transcriptional coactivator PGC-1α (peroxisome proliferator-activated receptor gamma coactivator-1α) and in cultured cells or gastrocnemius muscle. PPARδ and PGC-1α coprecipitated, which suggested that the thermogenic effects of PGC-1α may be mediated through interaction with PPARδ. PPARδ agonists may provide yet another target in the war against obesity. Y.-X. Wang, C.-H. Lee, S. Tiep, R. T. Yu, J. Ham, H. Kang, R. M. Evans, Peroxisome-proliferator-activated receptor δ activates fat metabolism to prevent obesity. Cell 113, 159-170 (2003). [Online Journal]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"70 1","pages":"TW165 - tw165"},"PeriodicalIF":0.0,"publicationDate":"2003-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80591898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-04-01DOI: 10.1126/scisignal.1762003tw127
The growth cones of developing neurons take s and turns that allow them to reach the appropriate target. Their path is guided by responses to attractive and repulsive cues from chemotropic ligands that they encounter along the way. These ligands activate receptors on the surface of the growth cone. Campbell and Holt describe new insights into the signaling pathways that are integrated to process such guidance cues. They report that in cultured Xenopus retinal growth cones, three different chemotropic ligands, netrin-1, semaphorin3A (Sema3A), and lysophosphatidic acid (LPA) stimulate distinct, but overlapping, signaling pathways. Netrin-1 and Sema3A activated the p42 and p44 mitogen-activated protein kinases (MAPKs). The p38 MAPK, normally associated with stress responses, was activated in cells treated with netrin-1 or LPA. Experiments with pharmacological inhibitors of the kinases indicated that the MAPK responses were necessary for axon guidance. Studies with antibodies to the active, cleaved form of caspase-3 revealed that caspase-3 was activated in response to LPA or netrin-1, and again, inhibitors were used to show that caspase activity was required for chemotropic responses in vitro. The authors discuss the potential role of caspase-3--better known as a component of pathways leading to apoptosis or cell death--in axon guidance. The authors further note similarities between the chemotropic pathways implicated in the present work with those thought to regulate synaptic plasticity. C. S. Campbell, C. E. Holt, Apoptotic pathway and MAPKs differentially regulate chemotropic responses of retinal growth cones. Neuron 37, 939-952 (2003). [Online Journal]
{"title":"Dissecting Growth Cone Guidance","authors":"","doi":"10.1126/scisignal.1762003tw127","DOIUrl":"https://doi.org/10.1126/scisignal.1762003tw127","url":null,"abstract":"The growth cones of developing neurons take s and turns that allow them to reach the appropriate target. Their path is guided by responses to attractive and repulsive cues from chemotropic ligands that they encounter along the way. These ligands activate receptors on the surface of the growth cone. Campbell and Holt describe new insights into the signaling pathways that are integrated to process such guidance cues. They report that in cultured Xenopus retinal growth cones, three different chemotropic ligands, netrin-1, semaphorin3A (Sema3A), and lysophosphatidic acid (LPA) stimulate distinct, but overlapping, signaling pathways. Netrin-1 and Sema3A activated the p42 and p44 mitogen-activated protein kinases (MAPKs). The p38 MAPK, normally associated with stress responses, was activated in cells treated with netrin-1 or LPA. Experiments with pharmacological inhibitors of the kinases indicated that the MAPK responses were necessary for axon guidance. Studies with antibodies to the active, cleaved form of caspase-3 revealed that caspase-3 was activated in response to LPA or netrin-1, and again, inhibitors were used to show that caspase activity was required for chemotropic responses in vitro. The authors discuss the potential role of caspase-3--better known as a component of pathways leading to apoptosis or cell death--in axon guidance. The authors further note similarities between the chemotropic pathways implicated in the present work with those thought to regulate synaptic plasticity. C. S. Campbell, C. E. Holt, Apoptotic pathway and MAPKs differentially regulate chemotropic responses of retinal growth cones. Neuron 37, 939-952 (2003). [Online Journal]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"83 1","pages":"TW127 - tw127"},"PeriodicalIF":0.0,"publicationDate":"2003-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74847931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-02-25DOI: 10.1126/scisignal.1712003tw83
Formation of long-term memory clearly requires transcriptional responses in neurons, but the identity of the expressed genes has been difficult to track down. Dubnau et al. used a combined strategy in which they analyzed DNA microarrays for transcripts whose abundance was increased during formation of long-term memories and also screened for Drosophila mutants with impaired long-term memory. Several genes that showed up in both screens encode proteins that take part in transport and localized translation of mRNA, a process already implicated in memory storage mechanisms. One gene, pumilio, works to repress translation of specific transcripts, and another, staufen, encodes a protein that functions in translocation of mRNAs. Studies with temperature-sensitive staufen mutants showed that loss of that gene product during a one-day period after training blocked memory formation, effectively ruling out other nonspecific actions of the staufen mutation. The authors propose that particles containing mRNAs are transported to synapses activated during the learning stimulus. Components like pumilio may repress translation along the way until the complex reaches its appropriate synaptic target. Greenspan provides insightful commentary and amusing historical background. J. Dubnau, A.-S. Chiang, L. Grady, J. Barditch, S. Gossweiler, J. McNeil, P. Smith, F. Buldoc, R. Scott, U. Certa, C. Broger, T. Tully, The staufen/pumilio pathway is involved in Drosophila long-term memory. Curr. Biol. 13, 286-296 (2003). [Online Journal] J. Greenspan, RNA and memory: From feeding to localization. Curr. Biol. 13, R126-R127 (2003). [Online Journal]
长期记忆的形成显然需要神经元的转录反应，但表达基因的身份一直难以追踪。Dubnau等人使用了一种组合策略，他们分析了在长期记忆形成过程中丰度增加的DNA微阵列转录本，并筛选了长期记忆受损的果蝇突变体。在两种筛选中都出现了一些基因，它们编码的蛋白质参与mRNA的转运和本地化翻译，这一过程已经与记忆储存机制有关。一个基因，pumilio，抑制特定转录物的翻译，另一个基因，staufen，编码一种在mrna易位中起作用的蛋白质。对温度敏感的staufen突变体的研究表明，在训练后的一天内，该基因产物的丢失会阻碍记忆的形成，有效地排除了staufen突变的其他非特异性作用。作者提出，含有mrna的颗粒被运输到学习刺激期间激活的突触。像pumilio这样的成分可能会一路上抑制翻译，直到复合物到达合适的突触目标。格林斯潘提供了深刻的评论和有趣的历史背景。杜诺，a - s。蒋，L. Grady, J. Barditch, S. Gossweiler, J. McNeil, P. Smith, F. Buldoc, R. Scott, U. Certa, C. Broger, T. Tully，果蝇长期记忆的staufen/pumilio通路研究。咕咕叫。生物学报，13,286-296(2003)。[网络期刊]J. Greenspan, RNA与记忆:从摄食到定位。咕咕叫。中国生物医学工程学报，2003,26(2):481 - 481。(在线期刊)
{"title":"Translating Memories","authors":"","doi":"10.1126/scisignal.1712003tw83","DOIUrl":"https://doi.org/10.1126/scisignal.1712003tw83","url":null,"abstract":"Formation of long-term memory clearly requires transcriptional responses in neurons, but the identity of the expressed genes has been difficult to track down. Dubnau et al. used a combined strategy in which they analyzed DNA microarrays for transcripts whose abundance was increased during formation of long-term memories and also screened for Drosophila mutants with impaired long-term memory. Several genes that showed up in both screens encode proteins that take part in transport and localized translation of mRNA, a process already implicated in memory storage mechanisms. One gene, pumilio, works to repress translation of specific transcripts, and another, staufen, encodes a protein that functions in translocation of mRNAs. Studies with temperature-sensitive staufen mutants showed that loss of that gene product during a one-day period after training blocked memory formation, effectively ruling out other nonspecific actions of the staufen mutation. The authors propose that particles containing mRNAs are transported to synapses activated during the learning stimulus. Components like pumilio may repress translation along the way until the complex reaches its appropriate synaptic target. Greenspan provides insightful commentary and amusing historical background. J. Dubnau, A.-S. Chiang, L. Grady, J. Barditch, S. Gossweiler, J. McNeil, P. Smith, F. Buldoc, R. Scott, U. Certa, C. Broger, T. Tully, The staufen/pumilio pathway is involved in Drosophila long-term memory. Curr. Biol. 13, 286-296 (2003). [Online Journal] J. Greenspan, RNA and memory: From feeding to localization. Curr. Biol. 13, R126-R127 (2003). [Online Journal]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"64 1","pages":"TW83 - tw83"},"PeriodicalIF":0.0,"publicationDate":"2003-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80182852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-02-18DOI: 10.1126/scisignal.1702003tw75
Scaffolding proteins contain binding sites for individual components of signal pathways and are thought to serve as grand organizing centers. Park et al. (see the Perspective by Ptashne and Gann) explored the basic physical requirements for a scaffold recruitment interaction using the yeast mitogen-activating protein kinase (MAPK) signaling pathways as a model system. Replacing defective scaffold-kinase recruitment interactions with completely different protein-protein interactions restored proper signaling, thus demonstrating the tremendous plasticity of these organizing factors. Such flexibility likely underlies the evolution of new pathways and resembles that of binding sites in transcription factors. S.-H. Park, A. Zarrinpar, W. A. Lim, Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms. Science 299, 1061-1064 (2003). [Abstract] [Full Text] M. Ptashne, A. Gann, Imposing specificity on kinases. Science 299, 1025-1027 (2003). [Summary] [Full Text]
支架蛋白包含信号通路中单个组分的结合位点，被认为是大的组织中心。Park等人(参见Ptashne和Gann的观点)利用酵母丝裂原激活蛋白激酶(MAPK)信号通路作为模型系统，探索了支架募集相互作用的基本物理要求。用完全不同的蛋白质相互作用取代有缺陷的支架激酶募集相互作用恢复了适当的信号传导，从而证明了这些组织因子的巨大可塑性。这种灵活性可能是新途径进化的基础，类似于转录因子结合位点的进化。工程学系。Park, A. Zarrinpar, W. A. Lim, Rewiring MAP激酶途径的替代支架组装机制。科学299,1061-1064(2003)。[摘要]M. Ptashne, A. Gann，强加特异性的激酶。科学299,1025-1027(2003)。【摘要】【全文】
{"title":"Flexible Management","authors":"","doi":"10.1126/scisignal.1702003tw75","DOIUrl":"https://doi.org/10.1126/scisignal.1702003tw75","url":null,"abstract":"Scaffolding proteins contain binding sites for individual components of signal pathways and are thought to serve as grand organizing centers. Park et al. (see the Perspective by Ptashne and Gann) explored the basic physical requirements for a scaffold recruitment interaction using the yeast mitogen-activating protein kinase (MAPK) signaling pathways as a model system. Replacing defective scaffold-kinase recruitment interactions with completely different protein-protein interactions restored proper signaling, thus demonstrating the tremendous plasticity of these organizing factors. Such flexibility likely underlies the evolution of new pathways and resembles that of binding sites in transcription factors. S.-H. Park, A. Zarrinpar, W. A. Lim, Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms. Science 299, 1061-1064 (2003). [Abstract] [Full Text] M. Ptashne, A. Gann, Imposing specificity on kinases. Science 299, 1025-1027 (2003). [Summary] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"24 1","pages":"TW75 - tw75"},"PeriodicalIF":0.0,"publicationDate":"2003-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83259742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-02-11DOI: 10.1126/scisignal.1692003tw65
The chloroplast, the light-converting energy factory of the plant cell, is a complex assemblage of proteins, of which only a portion are actually encoded within the chloroplast genome. The nucleus and the chloroplast thus must carry on a highly coordinated conversation not only to supply the chloroplast with its requisite components, but also to coordinate chloroplast function with other aspects of the cell's development and physiology. Encoded by the nucleus but resident in the plastid, the GUN4 protein is key to chlorophyll synthesis. Larkin et al. now find that GUN4 functions by controlling the synthesis of a signaling intermediate, Mg-protoporphyrin IX, through its actions on the Mg chelatase enzyme. R. M. Larkin, J. M. Alonso, J. R. Ecker, J. Chory, GUN4, a regulator of chlorophyll synthesis and intracellular signaling. Science 299, 902-906 (2003). [Abstract] [Full Text]
叶绿体是植物细胞的光转换能量工厂，是一个复杂的蛋白质组合，其中只有一部分实际上被编码在叶绿体基因组中。因此，细胞核和叶绿体必须进行高度协调的对话，不仅为叶绿体提供必需的成分，而且协调叶绿体与细胞发育和生理的其他方面的功能。GUN4蛋白由细胞核编码，但驻留在质体中，是叶绿素合成的关键。Larkin等人现在发现GUN4通过作用于Mg螯合酶来控制信号中间体Mg-原卟啉IX的合成。J. M. Larkin, J. M. Alonso, J. R. Ecker, J. Chory, GUN4:叶绿素合成和胞内信号转导的调控因子。科学299,902-906(2003)。【摘要】【全文】
{"title":"Chloroplast Synthesis Under the GUN","authors":"","doi":"10.1126/scisignal.1692003tw65","DOIUrl":"https://doi.org/10.1126/scisignal.1692003tw65","url":null,"abstract":"The chloroplast, the light-converting energy factory of the plant cell, is a complex assemblage of proteins, of which only a portion are actually encoded within the chloroplast genome. The nucleus and the chloroplast thus must carry on a highly coordinated conversation not only to supply the chloroplast with its requisite components, but also to coordinate chloroplast function with other aspects of the cell's development and physiology. Encoded by the nucleus but resident in the plastid, the GUN4 protein is key to chlorophyll synthesis. Larkin et al. now find that GUN4 functions by controlling the synthesis of a signaling intermediate, Mg-protoporphyrin IX, through its actions on the Mg chelatase enzyme. R. M. Larkin, J. M. Alonso, J. R. Ecker, J. Chory, GUN4, a regulator of chlorophyll synthesis and intracellular signaling. Science 299, 902-906 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"46 1","pages":"TW65 - tw65"},"PeriodicalIF":0.0,"publicationDate":"2003-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86830017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-01-14DOI: 10.1126/scisignal.1652003tw25
The parallel circulatory systems of blood and lymph separate during development through the differentiation of blood vessel endothelium. Abtahian et al. (see the Perspective by Jain and Padera) now show that this separation depends on specific intracellular signaling proteins--SLP-76 and Syk--known to be required for correct lymphocyte and platelet function. Abnormal connections between blood and lymphatic vessels occurred in mice lacking either protein and led to severe circulatory defects and hemorrhage. Surprisingly, expression of SLP-76 was not detected on endothelial cells, and abnormal connections occurred in wild-type mice that had been irradiated and received SLP-76-deficient bone marrow. These results suggest that cells of a hematopoietic lineage are required to help coordinate separation of the two vascular systems. F. Abtahian, A. Guerriero, E. Sebzda, M.-M. Lu, R. Zhou, A. Mocsai, E. E. Myers, B. Huang, D. G. Jackson, V. A. Ferrari, V. Tybulewicz, C. A. Lowell, J. J. Lepore, G. A. Koretzky, M. L. Kahn, Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 299, 247-251 (2003). [Abstract] [Full Text] R. K. Jain, T. P. Padera, Lymphatics make the break. Science 299, 209-210 (2003). [Summary] [Full Text]
平行的血液和淋巴循环系统在发育过程中通过血管内皮的分化而分离。Abtahian等人(参见Jain和Padera的观点)现在表明，这种分离依赖于特定的细胞内信号蛋白——SLP-76和Syk——已知是正确淋巴细胞和血小板功能所必需的。血液和淋巴管之间的异常连接在缺乏任何一种蛋白质的小鼠中发生，并导致严重的循环缺陷和出血。令人惊讶的是，在内皮细胞上未检测到SLP-76的表达，并且在照射和接受SLP-76缺陷骨髓的野生型小鼠中出现异常连接。这些结果表明，需要造血细胞谱系来帮助协调两个血管系统的分离。F. Abtahian, A. Guerriero, E. Sebzda, M.-M.。卢，周r .， A. Mocsai, E. E. Myers, B. Huang, D. G. Jackson, V. A. Ferrari, V. Tybulewicz, C. A. Lowell, J. J. Lepore, G. A. Koretzky, M. L. Kahn, SLP-76和Syk信号蛋白对血液和淋巴血管分离的调控。科学299,247-251(2003)。[摘要]R. K. Jain, T. P. Padera，《淋巴学的突破》。科学299,209-210(2003)。【摘要】【全文】
{"title":"Faulty Connections Between Circulatory Paths","authors":"","doi":"10.1126/scisignal.1652003tw25","DOIUrl":"https://doi.org/10.1126/scisignal.1652003tw25","url":null,"abstract":"The parallel circulatory systems of blood and lymph separate during development through the differentiation of blood vessel endothelium. Abtahian et al. (see the Perspective by Jain and Padera) now show that this separation depends on specific intracellular signaling proteins--SLP-76 and Syk--known to be required for correct lymphocyte and platelet function. Abnormal connections between blood and lymphatic vessels occurred in mice lacking either protein and led to severe circulatory defects and hemorrhage. Surprisingly, expression of SLP-76 was not detected on endothelial cells, and abnormal connections occurred in wild-type mice that had been irradiated and received SLP-76-deficient bone marrow. These results suggest that cells of a hematopoietic lineage are required to help coordinate separation of the two vascular systems. F. Abtahian, A. Guerriero, E. Sebzda, M.-M. Lu, R. Zhou, A. Mocsai, E. E. Myers, B. Huang, D. G. Jackson, V. A. Ferrari, V. Tybulewicz, C. A. Lowell, J. J. Lepore, G. A. Koretzky, M. L. Kahn, Regulation of blood and lymphatic vascular separation by signaling proteins SLP-76 and Syk. Science 299, 247-251 (2003). [Abstract] [Full Text] R. K. Jain, T. P. Padera, Lymphatics make the break. Science 299, 209-210 (2003). [Summary] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"110 1","pages":"TW25 - tw25"},"PeriodicalIF":0.0,"publicationDate":"2003-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87707590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-01-07DOI: 10.1126/scisignal.1642003tw13
Gene expression in mammalian cells is controlled by environmental and metabolic cues, but little is known about the molecular mechanisms that sense and respond to these cues. Dioum et al. (see the Perspective by Boehning and Snyder) have discovered one intriguing mechanism in a study of NPAS2 (neuronal PAS domain protein 2), a transcription factor implicated in the control of circadian rhythms. NPAS2 was shown to bind heme as a prosthetic group, and the heme, in turn, was shown to function as a gas-regulated sensor. In experiments with purified proteins, carbon monoxide (CO) was identified as a candidate ligand for this sensor. Exposure to CO inhibited the dimerization of NPAS2 with BMAL1, the protein that confers the transcription factor with DNA binding activity. E. M. Dioum, J. Rutter, J. R. Tuckerman, G. Gonzalez, M.-A. Gilles-Gonzalez, S. L. McKnight, NPAS2: A gas-responsive transcription factor. Science 298, 2385-2387 (2002). [Abstract] [Full Text] D. Boehning, S. H. Snyder, Carbon monoxide and clocks. Science 298, 2339-2340 (2002). [Summary] [Full Text]
哺乳动物细胞中的基因表达受环境和代谢信号的控制，但对感知和响应这些信号的分子机制知之甚少。Dioum等人(参见boeing和Snyder的观点)在对NPAS2(神经元PAS结构域蛋白2)的研究中发现了一个有趣的机制，NPAS2是一种涉及昼夜节律控制的转录因子。NPAS2被证明结合血红素作为一个假体基团，而血红素反过来又被证明是一个气体调节传感器。在纯化蛋白质的实验中，一氧化碳(CO)被确定为该传感器的候选配体。暴露于CO抑制了NPAS2与BMAL1的二聚化，BMAL1是赋予转录因子DNA结合活性的蛋白质。E. M. Dioum, J. Rutter, J. R. Tuckerman, G. Gonzalez, M. a。ggilles - gonzalez, S. L. McKnight, NPAS2:气体响应转录因子。科学298,2385-2387(2002)。[摘要][全文]D. boening, S. H. Snyder，一氧化碳与时钟。科学298,2339-2340(2002)。【摘要】【全文】
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Pub Date : 2003-01-07DOI: 10.1126/scisignal.1642003tw16
Changes in the numbers of olfactory neurons or in neuroblast migration to the olfactory bulb can affect abilities to discriminate odors or establish new odor-related memories. Studying female mice, Shingo et al. show that the hormone prolactin induces increased production of olfactory cell precursors. The prolactin-induced changes were apparent during pregnancy and also just after mating. Odor discrimination contributes to recognition of mates and offspring. These insights into prolactin-regulated neurogenesis may provide a physiological basis for understanding certain complex, seemingly social, behaviors. T. Shingo, C. Gregg, E. Enwere, H. Fujikawa, R. Hassam, C. Geary, J. C. Cross, S. Weiss, Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin. Science 299, 117-120 (2003). [Abstract] [Full Text]
嗅觉神经元数量的变化或神经母细胞向嗅球的迁移会影响辨别气味或建立新的气味相关记忆的能力。Shingo等人对雌性小鼠的研究表明，催乳素激素可诱导嗅觉细胞前体的产生增加。催乳素引起的变化在怀孕期间和刚交配后都很明显。气味辨别有助于识别配偶和后代。这些对催乳素调节的神经发生的见解可能为理解某些复杂的、看似社会的行为提供了生理基础。J. C. Cross, S. Weiss，催乳素对成年女性前脑神经发生的影响。科学学报，2003,17(4)。【摘要】【全文】
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Pub Date : 2002-12-10DOI: 10.1126/scisignal.1622002tw468
In vitro studies and work done in yeast have suggested that the transcription factor DRAP1 functions as a "general" transcriptional regulator that represses transcription by preventing the interaction of TFIIB with TBP (the TATA box-binding protein of TFIIB). Iratni et al. examined the function of DRAP1during early mouse development and found that the mutant embryo exhibited gastrulation defects consistent with increased activity of Nodal, a secreted morphogen of the transforming growth factor-β family that is the primary inducer of mesoderm during gastrulation. Nodal signaling is inhibited in the early embryo by DRAP1, most likely through its interaction with FoxH1. Thus, a factor that was previously thought to be a general transcriptional regulator displays a specific role in embryonic patterning through the regulation of Nodal's positive feedback loop, providing a mechanism for regulation of morphogen signaling. R. Iratni, Y.-T. Yan, C. Chen, J. Ding, Y. Zhang, S. M. Price, D. Reinberg, M. M. Shen, Inhibition of excess nodal signaling during mouse gastrulation by the transcriptional corepressor DRAP1. Science 298, 1996-1999 (2002). [Abstract] [Full Text]
体外研究和在酵母中完成的工作表明，转录因子DRAP1作为一种“一般”转录调节剂，通过阻止TFIIB与TBP (TFIIB的TATA盒结合蛋白)的相互作用来抑制转录。Iratni等研究了drap1在小鼠早期发育过程中的功能，发现突变胚胎表现出与Nodal活性增加一致的原肠形成缺陷，Nodal是转化生长因子-β家族的分泌形态原，是原肠形成过程中中胚层的主要诱导性因子。在早期胚胎中，节点信号被DRAP1抑制，很可能是通过它与FoxH1的相互作用。因此，一个先前被认为是一般转录调节因子的因子通过调节Nodal的正反馈回路在胚胎模式中显示出特定的作用，为形态素信号的调节提供了一种机制。r.i Iratni, y.t。陈春华，丁杰，张勇，Price, D. Reinberg，沈明明，转录共抑制因子DRAP1对小鼠原肠胚形成过程中过量节点信号的抑制作用。科学29,1996-1999(2002)。【摘要】【全文】
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Pub Date : 2002-12-03DOI: 10.1126/scisignal.1612002tw454
For normal organ and tissue development and function, certain genes must be expressed at the appropriate place and time. For example, neural genes must be expressed in neural tissue but shut down in nonneural tissues. Lunyak et al. examined mechanisms by which neural-specific gene expression can be restricted from nonneural tissues. The zinc-finger transcription factor REST/NRSF can mediate extraneural restriction through two different mechanisms, one of which uses active repression via a histone deacetylation complex and one that involves gene silencing via DNA methylation and the recruitment of the corepressor CoREST and silencing machinery. The latter mechanism can mediate gene silencing of specific chromosomal regions, including gene clusters encompassing neuron-specific genes, some of which do not themselves contain REST/NRSF response elements. V. V. Lunyak, R. Burgess, G. G. Prefontaine, C. Nelson, S.-H. Sze, J. Chenoweth, P. Schwartz, P. A. Pevzner, C. Glass, G. Mandel, M. G. Rosenfeld, Corepressor-dependent silencing of chromosomal regions encoding neuronal genes. Science 298, 1747-1752 (2002). [Abstract] [Full Text]
为了正常的器官和组织发育和功能，某些基因必须在适当的地点和时间表达。例如，神经基因必须在神经组织中表达，而在非神经组织中关闭。Lunyak等人研究了非神经组织限制神经特异性基因表达的机制。锌指转录因子REST/NRSF可以通过两种不同的机制介导神经外限制，一种是通过组蛋白去乙酰化复合物进行主动抑制，另一种是通过DNA甲基化和辅抑制因子CoREST的募集和沉默机制进行基因沉默。后一种机制可以介导特定染色体区域的基因沉默，包括包含神经元特异性基因的基因簇，其中一些基因簇本身不包含REST/NRSF反应元件。V. V. Lunyak, R. Burgess, G. G. Prefontaine, C. Nelson, s . h .。Sze, J. Chenoweth, P. Schwartz, P. A. Pevzner, C. Glass, G. Mandel, M. G. Rosenfeld，编码神经元基因的染色体区域依赖的沉默。科学298,1747-1752(2002)。【摘要】【全文】
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