Iron is an essential element for life on Earth and its shortage, or excess, in the living organism may lead to severe health disorders. Plants serve as the primary source of dietary iron and improving crop iron conten...Iron is an essential element for life on Earth and its shortage, or excess, in the living organism may lead to severe health disorders. Plants serve as the primary source of dietary iron and improving crop iron content is an important step towards a better public health. Our review focuses on the control of iron acquisition in dicotyledonous plants and monocots that apply a reduction-based strategy in order to mobilize and import iron from the rhizosphere. Achieving a balance between shortage and excess of iron requires a tight regulation of the activity of the iron uptake system. A number of studies, ranging from single gene characterization to systems biology analyses, have led to the rapid expansion of our knowledge on iron uptake in recent years. Here, we summarize the novel insights into the regulation of iron ac- quisition and internal mobilization from intracellular stores. We present a detailed view of the main known regulatory networks defined by the Arabidopsis regulators FIT and POPEYE （PYE）. Additionally, we analyze the root and leaf iron- responsive regulatory networks, revealing novel potential gene interactions and reliable iron-deficiency marker genes. We discuss perspectives and open questions with regard to iron sensing and post-translational regulation.展开更多
Pancreatic cancer is one of the most lethal malignancies.Significant progresses have been made in understanding of pancreatic cancer pathogenesis,including appreciation of precursor lesions or premalignant pancreatic ...Pancreatic cancer is one of the most lethal malignancies.Significant progresses have been made in understanding of pancreatic cancer pathogenesis,including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia(PanINs),description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior.However,the currently used therapeutic strategies targeting tumor epithelial cells,which are potent in cell culture and animal models,have not been successful in the clinic.Presumably,therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis,which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression.Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies.This review focuses on the origination,evolution and disruption of stromal molecular and cellular components in pancreatic cancer,and their biological effects on pancreatic cancer pathogenesis.展开更多
Identification of all genes involved in the phytochrome （phy）-medieted responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth end developm...Identification of all genes involved in the phytochrome （phy）-medieted responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth end development. This article highlights end integrates the central findings of two recent comprehensive studies in Arabidopsis that have identified the genome-wide set of phy-reguleted genes that respond rapidly to red-light signals upon first exposure of dark-grown seedlings, and have tested the functional relevance to normal seedling photomorphogenesis of an Initial subset of these genes. The data： （a） reveal considerable complexity in the channeling of the light signals through the different phy-femily members （phyA to phyE） to responsive genes; （b） identify a diversity of transcription-factor-encoding genes as major early, if not primary, targets of phy signaling, end, therefore, as potentially important regulators in the transcriptional-network hierarchy; and （c） identify auxin-related genes as the dominant class among rapidly-regulated, hormone-related genes. However, reverse-genetic functional profiling of a selected subset of these genes reveals that only a limited fraction are necessary for optimal phy-induced seedling deetioletion.展开更多
乳腺癌耐药蛋白(Breast cancer resistance protein,BCRP),又名ABCG2,是ATP结合盒(ATP-binding cas-sette,ABC)转运蛋白超家族成员之一,在肿瘤多药耐药中具有十分重要的作用。BCRP基因启动子区无TATA盒,含CAAT盒、AP1位点、AP2位点以及...乳腺癌耐药蛋白(Breast cancer resistance protein,BCRP),又名ABCG2,是ATP结合盒(ATP-binding cas-sette,ABC)转运蛋白超家族成员之一,在肿瘤多药耐药中具有十分重要的作用。BCRP基因启动子区无TATA盒,含CAAT盒、AP1位点、AP2位点以及CpG岛下游的多个Sp-1位点。近年来的研究发现,转录因子孕激素受体(PR)、雌激素受体(ER)、核因子-κB(NF-κB)、缺氧诱导因子(HIF)、Nrf2、芳香烃受体(AhR)、过氧化物酶体增殖活化受体(PPAR)和KLF5等可与BCRP启动子或增强子区的特定反应元件结合进而激活BCRP的转录。促炎细胞因子、生长因子、同源盒基因MSX2、Sonic hedgehog信号通路、Notch信号通路和RAR/RXR信号通路等均参与了BCRP的转录调控。此外,启动子甲基化和组蛋白乙酰化在BCRP转录调控尤其是药物诱导BCRP表达中发挥重要作用。文章综述了这一研究领域的进展,着重讨论了转录因子及表观遗传学在BCRP转录调控中的作用。展开更多
Myostatin (GDF8, MSTN) is a member of the transforming growth factor beta su- perfamily that is essential for proper regulation of skeletal muscle mass. In order to study its ex- pression and regulatory mechanism deep...Myostatin (GDF8, MSTN) is a member of the transforming growth factor beta su- perfamily that is essential for proper regulation of skeletal muscle mass. In order to study its ex- pression and regulatory mechanism deeply, we have presented a comparative analysis of about 170-kb pig BAC sequence containing the myostatin gene among pig, human and mouse. The genomic region is characterized by high interspersed repeats and low G+C content. As for the myostatin gene, a higher sequence similarity is found between human and pig than between these species and the mouse. One striking feature is that the structure of two TATA-boxes in the nearby downstream of CCAAT-box is identified in the promoter. Further analysis reveals that the TATA-box1 is responsible for the transcription in pig and human, but the TATA-box2 acts on the transcription in mouse. The other interesting feature is that two polyadenylation signal sequences (AATAAA) exist in 3′UTR of the pig myostatin gene. Moreover, a large number of potential tran- scription factor-binding sites are also identified in evolutionary conserved regions (ECRs), which may be associated with the regulation of myostatin. Many putative transcription factors play an important role in the muscle development, and the complex interaction between myostatin and these factors may be required for proper muscle development.展开更多
The availability of soil phosphorus （P）, an essential element, is one of the most important requirements for plant growth and crop production. The morphological and physiological adaptations evolved by plants to cop...The availability of soil phosphorus （P）, an essential element, is one of the most important requirements for plant growth and crop production. The morphological and physiological adaptations evolved by plants to cope with P starvation have been well characterized. Several P deficiency plant responses are regulated at the transcriptional level. Microarray analysis has generated valuable information on global gene expression in Arabidopsis thaliana grown under P-stress. Despite the identification of P responsive genes, little is known about the regulation of gene expression changes. Four transcription factors, PHRI, WRKY75, ZAT6 and BHLH32, involved in P starvation signaling have been characterized in Arabidopsis, and signaling pathways are deciphered. This review analyzes the current knowledge of transcriptional regulation of P starvation responses in Arabidopsis vis-a-vis legumes such as lupine, common bean and Medicago truncatula. The knowledge on regulatory and signaling mechanisms involved in P acquisition and use in legumes will be useful for improvement of these crops, which account for a large proportion of the world＇s crop production, providing good nutritional quality feed and food.展开更多
Both embryonic and adult neurogenesis involves the self-renewal/proliferation, survival, migration and lineage differentiation of neural stem/progenitor cells. Such dynamic process is tightly regulated by intrinsic an...Both embryonic and adult neurogenesis involves the self-renewal/proliferation, survival, migration and lineage differentiation of neural stem/progenitor cells. Such dynamic process is tightly regulated by intrinsic and extrinsic factors and complex signaling pathways. Misregulated neurogenesis contributes much to a large range of neurodevelopmental defects and neurodegenerative diseases. The signaling of NFKB regulates many genes important in inflammation, immunity, cell survival and neural plasticity. During neurogenesis, NFKB signaling mediates the effect of numerous niche factors such as cytokines, chemokines, growth factors, extracellular matrix molecules, but also cross- talks with other signaling pathways such as Notch, Shh, Wnt/l]-catenin. This review summarizes current progress on the NFttB signaling in all aspects of neurogenesis, focusing on the novel role of NFKB signaling in initiating early neural differentiation of neural stem cells and embryonic stem ceils.展开更多
文摘Iron is an essential element for life on Earth and its shortage, or excess, in the living organism may lead to severe health disorders. Plants serve as the primary source of dietary iron and improving crop iron content is an important step towards a better public health. Our review focuses on the control of iron acquisition in dicotyledonous plants and monocots that apply a reduction-based strategy in order to mobilize and import iron from the rhizosphere. Achieving a balance between shortage and excess of iron requires a tight regulation of the activity of the iron uptake system. A number of studies, ranging from single gene characterization to systems biology analyses, have led to the rapid expansion of our knowledge on iron uptake in recent years. Here, we summarize the novel insights into the regulation of iron ac- quisition and internal mobilization from intracellular stores. We present a detailed view of the main known regulatory networks defined by the Arabidopsis regulators FIT and POPEYE （PYE）. Additionally, we analyze the root and leaf iron- responsive regulatory networks, revealing novel potential gene interactions and reliable iron-deficiency marker genes. We discuss perspectives and open questions with regard to iron sensing and post-translational regulation.
基金The work was supported in part by grants R01-CA129956,R01-CA148954,R01CA152309 and R01CA172233(to K.Xie)from the National Cancer Institute,National Institutes of HealthThis research is supported in part by the National Institutes of Health through MD Anderson’s Cancer Center Support Grant CA016672.
文摘Pancreatic cancer is one of the most lethal malignancies.Significant progresses have been made in understanding of pancreatic cancer pathogenesis,including appreciation of precursor lesions or premalignant pancreatic intraepithelial neoplasia(PanINs),description of sequential transformation from normal pancreatic tissue to invasive pancreatic cancer and identification of major genetic and epigenetic events and the biological impact of those events on malignant behavior.However,the currently used therapeutic strategies targeting tumor epithelial cells,which are potent in cell culture and animal models,have not been successful in the clinic.Presumably,therapeutic resistance of pancreatic cancer is at least in part due to its drastic desmoplasis,which is a defining hallmark for and circumstantially contributes to pancreatic cancer development and progression.Improved understanding of the dynamic interaction between cancer cells and the stroma is important to better understanding pancreatic cancer biology and to designing effective intervention strategies.This review focuses on the origination,evolution and disruption of stromal molecular and cellular components in pancreatic cancer,and their biological effects on pancreatic cancer pathogenesis.
基金Supported by National Institute of Health Grant GM47475, Department of Energy Grant DE-FG03-87ER13742, and U.S. Department of Agriculture Grant 5335-21000-010-00D. Publication of this paper is supported by the National Natural Science Foundation of China （30624808） and Science Publication Foundation of the Chinese Academy of Sciences.Acknowledgements Thank the coauthors of the original research publications used as the basis for this article, and Jim Tepperman for figure preparation and help with the manuscript.
文摘Identification of all genes involved in the phytochrome （phy）-medieted responses of plants to their light environment is an important goal in providing an overall understanding of light-regulated growth end development. This article highlights end integrates the central findings of two recent comprehensive studies in Arabidopsis that have identified the genome-wide set of phy-reguleted genes that respond rapidly to red-light signals upon first exposure of dark-grown seedlings, and have tested the functional relevance to normal seedling photomorphogenesis of an Initial subset of these genes. The data： （a） reveal considerable complexity in the channeling of the light signals through the different phy-femily members （phyA to phyE） to responsive genes; （b） identify a diversity of transcription-factor-encoding genes as major early, if not primary, targets of phy signaling, end, therefore, as potentially important regulators in the transcriptional-network hierarchy; and （c） identify auxin-related genes as the dominant class among rapidly-regulated, hormone-related genes. However, reverse-genetic functional profiling of a selected subset of these genes reveals that only a limited fraction are necessary for optimal phy-induced seedling deetioletion.
基金The sequence data described in this paper have been submitted to GenBank under accession No. AY208121.
文摘Myostatin (GDF8, MSTN) is a member of the transforming growth factor beta su- perfamily that is essential for proper regulation of skeletal muscle mass. In order to study its ex- pression and regulatory mechanism deeply, we have presented a comparative analysis of about 170-kb pig BAC sequence containing the myostatin gene among pig, human and mouse. The genomic region is characterized by high interspersed repeats and low G+C content. As for the myostatin gene, a higher sequence similarity is found between human and pig than between these species and the mouse. One striking feature is that the structure of two TATA-boxes in the nearby downstream of CCAAT-box is identified in the promoter. Further analysis reveals that the TATA-box1 is responsible for the transcription in pig and human, but the TATA-box2 acts on the transcription in mouse. The other interesting feature is that two polyadenylation signal sequences (AATAAA) exist in 3′UTR of the pig myostatin gene. Moreover, a large number of potential tran- scription factor-binding sites are also identified in evolutionary conserved regions (ECRs), which may be associated with the regulation of myostatin. Many putative transcription factors play an important role in the muscle development, and the complex interaction between myostatin and these factors may be required for proper muscle development.
基金Supported by Dirección General de Asuntos del Personal Acadmico/UNAM(General Directorate of Academic Staff Affairs/UNAM), Me'xico (grant no.PAPIIT: IN211607).
文摘The availability of soil phosphorus （P）, an essential element, is one of the most important requirements for plant growth and crop production. The morphological and physiological adaptations evolved by plants to cope with P starvation have been well characterized. Several P deficiency plant responses are regulated at the transcriptional level. Microarray analysis has generated valuable information on global gene expression in Arabidopsis thaliana grown under P-stress. Despite the identification of P responsive genes, little is known about the regulation of gene expression changes. Four transcription factors, PHRI, WRKY75, ZAT6 and BHLH32, involved in P starvation signaling have been characterized in Arabidopsis, and signaling pathways are deciphered. This review analyzes the current knowledge of transcriptional regulation of P starvation responses in Arabidopsis vis-a-vis legumes such as lupine, common bean and Medicago truncatula. The knowledge on regulatory and signaling mechanisms involved in P acquisition and use in legumes will be useful for improvement of these crops, which account for a large proportion of the world＇s crop production, providing good nutritional quality feed and food.
文摘Both embryonic and adult neurogenesis involves the self-renewal/proliferation, survival, migration and lineage differentiation of neural stem/progenitor cells. Such dynamic process is tightly regulated by intrinsic and extrinsic factors and complex signaling pathways. Misregulated neurogenesis contributes much to a large range of neurodevelopmental defects and neurodegenerative diseases. The signaling of NFKB regulates many genes important in inflammation, immunity, cell survival and neural plasticity. During neurogenesis, NFKB signaling mediates the effect of numerous niche factors such as cytokines, chemokines, growth factors, extracellular matrix molecules, but also cross- talks with other signaling pathways such as Notch, Shh, Wnt/l]-catenin. This review summarizes current progress on the NFttB signaling in all aspects of neurogenesis, focusing on the novel role of NFKB signaling in initiating early neural differentiation of neural stem cells and embryonic stem ceils.
