Phytochromes are red and far-red light photoreceptors that play fundamental roles in controlling many aspects of plant growth and development in response to light. The past two decades have witnessed the mechanistic e...Phytochromes are red and far-red light photoreceptors that play fundamental roles in controlling many aspects of plant growth and development in response to light. The past two decades have witnessed the mechanistic elucidation of the action mode of phytochromes, including their regulation by external and endogenous factors and how they exert their function as transcriptional regulators. More importantly, recent advances have substantially deepened our understanding on the integration of the phytochromemediated signal into other cellular and developmental processes, such as elongation of hypocotyls, shoot branching, circadian clock, and flowering time, which ofteninvolves complex intercellular and interorgan signaling. Based on these advances, this review illustrates a blueprint of our current understanding of phytochrome signaling and its crosstalk with other signaling pathways, and also points out still open questions that need to be addressed in the future.展开更多
Maintenance of homeostasis is pivotal to all forms of life. In the case of plants, homeostasis is constantly threatened by the inability to escape environmental fluctuations, and therefore sensitive mechanisms must ha...Maintenance of homeostasis is pivotal to all forms of life. In the case of plants, homeostasis is constantly threatened by the inability to escape environmental fluctuations, and therefore sensitive mechanisms must have evolved to allow rapid perception of environmental cues and concomitant modification of growth and developmental patterns for adaptation and survival. Re-establishment of homeostasis in response to environmental perturbations requires reprog- ramming of metabolism and gene expression to shunt energy sources from growth-related biosynthetic processes to defense, acclimation, and, ultimately, adaptation. Failure to mount an initial 'emergency' response may result in nutrient deprivation and irreversible senescence and cell death. Early signaling events largely determine the capacity of plants to orchestrate a successful adaptive response. Early events, on the other hand, are likely to be shared by different conditions through the generation of similar signals and before more specific responses are elaborated. Recent studies lend credence to this hypothesis, underpinning the importance of a shared energy signal in the transcriptional response to various types of stress. Energy deficiency is associated with most environmental perturbations due to their direct or indirect deleterious impact on photosynthesis and/or respiration. Several systems are known to have evolved for monitoring the available resources and triggering metabolic, growth, and developmental decisions accordingly. In doing so, energy-sensing systems regulate gene expression at multiple levels to allow flexibility in the diversity and the kinetics of the stress response.展开更多
The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology. Almost a decade ago, the discovery of the Hippo signaling pathway in Drosophila shed som...The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology. Almost a decade ago, the discovery of the Hippo signaling pathway in Drosophila shed some light on this puzzling issue. The Hippo signaling pathway is highly conserved in both invertebrates and vertebrates, and plays critical roles in animal development. It controls organ size and growth by inhibiting cell proliferation and by promoting apoptosis. Malfunction of the Hippo signaling pathway leads to cancer development and tumorigenesis. Although the core of the signaling pathway is well understood, the upstream inputs and downstream transcriptional regulation are still obscure to us. In this review, we summarize the current understanding of the mechanism and the function of the Hippo signaling pathway and compare its differences between flies and mammals. We underline the crosstalk between the Hippo signaling pathway and other signaling pathways, and the possible roles of the Hippo pathway in stem cell proliferation and self-renewal.展开更多
The interplay between host cell genetics and Epstein-Barr virus(EBV) infection contributes to the development of nasopharyngeal carcinoma(NPC). Understanding the host genetic and epigenetic alterations and the influen...The interplay between host cell genetics and Epstein-Barr virus(EBV) infection contributes to the development of nasopharyngeal carcinoma(NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen(HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.展开更多
The stress-associated protein SAP12 belongs to the stress-associated protein (SAP) family with 14 members in Arabidopsis thaliana. SAP12 contains two AN1 zinc fingers and was identified in diagonal 2D redox SDS-PAGE...The stress-associated protein SAP12 belongs to the stress-associated protein (SAP) family with 14 members in Arabidopsis thaliana. SAP12 contains two AN1 zinc fingers and was identified in diagonal 2D redox SDS-PAGE as a protein undergoing major redox-dependent conformational changes. Its transcript was strongly induced under cold and salt stress in a time-dependent manner similar to SAP10, with high levels after 6 h and decreasing levels after 24 and 48 h. The tran- script regulation resembled those of the stress marker peroxiredoxin PrxllD at 24 and 48 h. Recombinant SAP12 protein showed redox-dependent changes in quaternary structure as visualized by altered electrophoretic mobility in non-reducing SDS polyacrylamide gel electrophoresis. The oxidized oligomer was reduced by high dithiothreitol concentrations, and also by E. coli thioredoxin TrxA with low dithiothreitol (DTF) concentrations or NADPH plus NADPH-dependent thioredoxin reductase. From Western blots, the SAP12 protein amount was estimated to be in the range of 0.5 ngμg^-1 leaf protein. SAP12 protein decreased under salt and cold stress. These data suggest a redox state-linked function of SAP12 in plant cells particularly under cold and salt stress.展开更多
病毒入侵机体后,会被天然免疫系统所识别,进而引发天然免疫信号通路的活化产生一型干扰素(IFNα/β)和一些炎性细胞因子如IL-1β。目前研究发现,病毒入侵信号主要由一类模式识别受体识别,包括Toll样受体(Toll like receptors,TLRs)、RI...病毒入侵机体后,会被天然免疫系统所识别,进而引发天然免疫信号通路的活化产生一型干扰素(IFNα/β)和一些炎性细胞因子如IL-1β。目前研究发现,病毒入侵信号主要由一类模式识别受体识别,包括Toll样受体(Toll like receptors,TLRs)、RIG-I样受体(RIG-I like receptors,RLRs)、Nod样受体(Nod like receptors,NLRs)、Hin-200家族蛋白及一些DNA受体,这些受体介导一型干扰素及炎性细胞因子的产生,并受到多种严格的调控机制调控。该文将对模式识别受体介导的抗病毒天然免疫信号转导通路及相关调控分子机制做一综述。展开更多
AUXIN BINDING PROTEIN 1 (ABP1) has long been proposed as an auxin receptor to regulate cell expansion. The embryo lethality of ABP1-null mutants demonstrates its fundamental role in plant development, but also hinde...AUXIN BINDING PROTEIN 1 (ABP1) has long been proposed as an auxin receptor to regulate cell expansion. The embryo lethality of ABP1-null mutants demonstrates its fundamental role in plant development, but also hinders investigation of its involvement in post-embryonic processes and its mode of action. By taking advantage of weak alleles and inducible systems, several recent studies have revealed a role for ABP1 in organ development, cell polarization, and shape formation. In addition to its role in the regulation of auxin-induced gene expression, ABP1 has now been shown to modulate non-transcriptional auxin responses. ABP1 is required for activating two antagonizing ROP GTPase signaling pathways involved in cytoskeletal reorganization and cell shape formation, and participates in the regulation of clathrinmediated endocytosis to subsequently affect PIN protein distribution. These exciting discoveries provide indisputable evidence for the auxin-induced signaling pathways that are downstream of ABP1 function, and suggest intriguing mechanisms for ABPl-mediated polar cell expansion and spatial coordination in response to auxin.展开更多
Somatic embryogenesis receptor-like kinases (SERKs) are leucine-rich repeat receptor-like kinases involved in several, seemingly unrelated, plant-signaling pathways. In Arabidopsis thaliana, functional and genetic a...Somatic embryogenesis receptor-like kinases (SERKs) are leucine-rich repeat receptor-like kinases involved in several, seemingly unrelated, plant-signaling pathways. In Arabidopsis thaliana, functional and genetic analysis of four SERK proteins has indicated that they are only partly redundant; their functions overlap but each performs a specific subset of signaling roles. The molecular basis for the functional spec- ificity within this highly homologous protein family is currently not known. Sequence analysis of SERK pro- teins from different plant species indicates that the SERKs are a highly conserved protein family present in monocots, dicots, and non-vascular plants. Residues in the extracellular domain that are important for interaction with other receptor kinases are highly conserved, even among SERK members without a func- tion in the corresponding pathways. SERK2, for instance, does not function in the brassinosteroid pathway, does not interact with BRI1, but is conserved in its BRIl-interacting domain. Further sequence analysis indicates that SERK3/BAK1 and SERK4/BKK1 have diverged from the original SERK protein in both their extracellular and cytoplasmic domains. Functional analysis of chimeric SERK proteins shows that different domains provide the SERK proteins with different functional specificity. For instance, the SERK1 or SERK2 extracellular domains are essential for SERK function in male sporogenesis, while the SERK3 extracellular and cytoplasmic domains are essential for SERK3 activity in brassinosteroid and flagellin signaling. The emerging picture is that SERKs are ancient genes, whose products have been recruited as co-receptors in the newly evolved signaling pathways. The SERK ligand-binding and protein-protein interaction domains are highly conserved, allowing all SERKs to form complexes, albeit with different affinity. However, specific functional residues must have been altered, in both the extracellular and intracellular domains, to allow for the observed differences in functionality展开更多
附着胞的分化、形成和成熟是稻瘟病菌成功侵入寄主的前提.稻瘟病菌识别不同的胞外信号,可通过环化腺苷酸(cAMP)信号途径、丝分裂原激活蛋白激酶(Mitogen-activated protein kinase,MAPK)信号转导途径和Ca2+信号途径等不同的信号途径来...附着胞的分化、形成和成熟是稻瘟病菌成功侵入寄主的前提.稻瘟病菌识别不同的胞外信号,可通过环化腺苷酸(cAMP)信号途径、丝分裂原激活蛋白激酶(Mitogen-activated protein kinase,MAPK)信号转导途径和Ca2+信号途径等不同的信号途径来调控附着胞发育.结合这些信号传递途径相关基因及其信号途径间关系的研究论述了调控稻瘟病菌附着胞分化和发育的信号传递的分子机理.展开更多
Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes in...Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.展开更多
HER3 belongs to the human epidermal growth factor receptor(HER) family which also includes HER1/EGFR/erb B1,HER2/erb B2,and HER4/erb B4. As a unique member of the HER family,HER3 lacks or has little intrinsic tyrosine...HER3 belongs to the human epidermal growth factor receptor(HER) family which also includes HER1/EGFR/erb B1,HER2/erb B2,and HER4/erb B4. As a unique member of the HER family,HER3 lacks or has little intrinsic tyrosine kinase activity. It frequently co-expresses and forms heterodimers with other receptor tyrosine kinases(RTKs) in cancer cells to activate oncogenic signaling,especially the PI-3 K/Akt pathway and Src kinase. Elevated expression of HER3 has been observed in a wide variety of human cancers and associates with a worse survival in cancer patients with solid tumors.Studies on the underlying mechanism implicate HER3 expression as a major cause of treatment failure in cancer therapy. Activation of HER3 signaling has also been shown to promote cancer metastasis. These data strongly support the notion that therapeutic inactivation of HER3 and/or its downstream signaling is required to overcome treatment resistance and improve the outcomes of cancer patients.展开更多
基金Research in the authors' laboratory is supported by National Science Foundations of China (NSFC) project 31430008 to Haiyang Wang.ACKNOWLEDGMENTS We apologize to the colleagues whose work or original publications could not be cited because of space limitations. No conflict of interest declared.
文摘Phytochromes are red and far-red light photoreceptors that play fundamental roles in controlling many aspects of plant growth and development in response to light. The past two decades have witnessed the mechanistic elucidation of the action mode of phytochromes, including their regulation by external and endogenous factors and how they exert their function as transcriptional regulators. More importantly, recent advances have substantially deepened our understanding on the integration of the phytochromemediated signal into other cellular and developmental processes, such as elongation of hypocotyls, shoot branching, circadian clock, and flowering time, which ofteninvolves complex intercellular and interorgan signaling. Based on these advances, this review illustrates a blueprint of our current understanding of phytochrome signaling and its crosstalk with other signaling pathways, and also points out still open questions that need to be addressed in the future.
文摘Maintenance of homeostasis is pivotal to all forms of life. In the case of plants, homeostasis is constantly threatened by the inability to escape environmental fluctuations, and therefore sensitive mechanisms must have evolved to allow rapid perception of environmental cues and concomitant modification of growth and developmental patterns for adaptation and survival. Re-establishment of homeostasis in response to environmental perturbations requires reprog- ramming of metabolism and gene expression to shunt energy sources from growth-related biosynthetic processes to defense, acclimation, and, ultimately, adaptation. Failure to mount an initial 'emergency' response may result in nutrient deprivation and irreversible senescence and cell death. Early signaling events largely determine the capacity of plants to orchestrate a successful adaptive response. Early events, on the other hand, are likely to be shared by different conditions through the generation of similar signals and before more specific responses are elaborated. Recent studies lend credence to this hypothesis, underpinning the importance of a shared energy signal in the transcriptional response to various types of stress. Energy deficiency is associated with most environmental perturbations due to their direct or indirect deleterious impact on photosynthesis and/or respiration. Several systems are known to have evolved for monitoring the available resources and triggering metabolic, growth, and developmental decisions accordingly. In doing so, energy-sensing systems regulate gene expression at multiple levels to allow flexibility in the diversity and the kinetics of the stress response.
基金supported by the grants from the National Natural Science Foundation of China(No.30971646)the National Basic Research Program of China(973 Program No. 2010CB912100)+2 种基金the National Key Basic Research and Development Program of China(No.2011CB915502)the"Strategic Priority Research Program"of the Chinese Academy of Sciences(No.XDA01010406)L.Z.is the scholar of the Hundred Talents Program of the Chinese Academy of Sciences
文摘The molecular mechanisms of organ size control and regulation remain one of the major unsolved mysteries of development biology. Almost a decade ago, the discovery of the Hippo signaling pathway in Drosophila shed some light on this puzzling issue. The Hippo signaling pathway is highly conserved in both invertebrates and vertebrates, and plays critical roles in animal development. It controls organ size and growth by inhibiting cell proliferation and by promoting apoptosis. Malfunction of the Hippo signaling pathway leads to cancer development and tumorigenesis. Although the core of the signaling pathway is well understood, the upstream inputs and downstream transcriptional regulation are still obscure to us. In this review, we summarize the current understanding of the mechanism and the function of the Hippo signaling pathway and compare its differences between flies and mammals. We underline the crosstalk between the Hippo signaling pathway and other signaling pathways, and the possible roles of the Hippo pathway in stem cell proliferation and self-renewal.
基金supported by the Research Grants Council Area of Excellence grant (AoE/M-06/08)
文摘The interplay between host cell genetics and Epstein-Barr virus(EBV) infection contributes to the development of nasopharyngeal carcinoma(NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen(HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.
文摘The stress-associated protein SAP12 belongs to the stress-associated protein (SAP) family with 14 members in Arabidopsis thaliana. SAP12 contains two AN1 zinc fingers and was identified in diagonal 2D redox SDS-PAGE as a protein undergoing major redox-dependent conformational changes. Its transcript was strongly induced under cold and salt stress in a time-dependent manner similar to SAP10, with high levels after 6 h and decreasing levels after 24 and 48 h. The tran- script regulation resembled those of the stress marker peroxiredoxin PrxllD at 24 and 48 h. Recombinant SAP12 protein showed redox-dependent changes in quaternary structure as visualized by altered electrophoretic mobility in non-reducing SDS polyacrylamide gel electrophoresis. The oxidized oligomer was reduced by high dithiothreitol concentrations, and also by E. coli thioredoxin TrxA with low dithiothreitol (DTF) concentrations or NADPH plus NADPH-dependent thioredoxin reductase. From Western blots, the SAP12 protein amount was estimated to be in the range of 0.5 ngμg^-1 leaf protein. SAP12 protein decreased under salt and cold stress. These data suggest a redox state-linked function of SAP12 in plant cells particularly under cold and salt stress.
文摘病毒入侵机体后,会被天然免疫系统所识别,进而引发天然免疫信号通路的活化产生一型干扰素(IFNα/β)和一些炎性细胞因子如IL-1β。目前研究发现,病毒入侵信号主要由一类模式识别受体识别,包括Toll样受体(Toll like receptors,TLRs)、RIG-I样受体(RIG-I like receptors,RLRs)、Nod样受体(Nod like receptors,NLRs)、Hin-200家族蛋白及一些DNA受体,这些受体介导一型干扰素及炎性细胞因子的产生,并受到多种严格的调控机制调控。该文将对模式识别受体介导的抗病毒天然免疫信号转导通路及相关调控分子机制做一综述。
文摘AUXIN BINDING PROTEIN 1 (ABP1) has long been proposed as an auxin receptor to regulate cell expansion. The embryo lethality of ABP1-null mutants demonstrates its fundamental role in plant development, but also hinders investigation of its involvement in post-embryonic processes and its mode of action. By taking advantage of weak alleles and inducible systems, several recent studies have revealed a role for ABP1 in organ development, cell polarization, and shape formation. In addition to its role in the regulation of auxin-induced gene expression, ABP1 has now been shown to modulate non-transcriptional auxin responses. ABP1 is required for activating two antagonizing ROP GTPase signaling pathways involved in cytoskeletal reorganization and cell shape formation, and participates in the regulation of clathrinmediated endocytosis to subsequently affect PIN protein distribution. These exciting discoveries provide indisputable evidence for the auxin-induced signaling pathways that are downstream of ABP1 function, and suggest intriguing mechanisms for ABPl-mediated polar cell expansion and spatial coordination in response to auxin.
文摘Somatic embryogenesis receptor-like kinases (SERKs) are leucine-rich repeat receptor-like kinases involved in several, seemingly unrelated, plant-signaling pathways. In Arabidopsis thaliana, functional and genetic analysis of four SERK proteins has indicated that they are only partly redundant; their functions overlap but each performs a specific subset of signaling roles. The molecular basis for the functional spec- ificity within this highly homologous protein family is currently not known. Sequence analysis of SERK pro- teins from different plant species indicates that the SERKs are a highly conserved protein family present in monocots, dicots, and non-vascular plants. Residues in the extracellular domain that are important for interaction with other receptor kinases are highly conserved, even among SERK members without a func- tion in the corresponding pathways. SERK2, for instance, does not function in the brassinosteroid pathway, does not interact with BRI1, but is conserved in its BRIl-interacting domain. Further sequence analysis indicates that SERK3/BAK1 and SERK4/BKK1 have diverged from the original SERK protein in both their extracellular and cytoplasmic domains. Functional analysis of chimeric SERK proteins shows that different domains provide the SERK proteins with different functional specificity. For instance, the SERK1 or SERK2 extracellular domains are essential for SERK function in male sporogenesis, while the SERK3 extracellular and cytoplasmic domains are essential for SERK3 activity in brassinosteroid and flagellin signaling. The emerging picture is that SERKs are ancient genes, whose products have been recruited as co-receptors in the newly evolved signaling pathways. The SERK ligand-binding and protein-protein interaction domains are highly conserved, allowing all SERKs to form complexes, albeit with different affinity. However, specific functional residues must have been altered, in both the extracellular and intracellular domains, to allow for the observed differences in functionality
文摘附着胞的分化、形成和成熟是稻瘟病菌成功侵入寄主的前提.稻瘟病菌识别不同的胞外信号,可通过环化腺苷酸(cAMP)信号途径、丝分裂原激活蛋白激酶(Mitogen-activated protein kinase,MAPK)信号转导途径和Ca2+信号途径等不同的信号途径来调控附着胞发育.结合这些信号传递途径相关基因及其信号途径间关系的研究论述了调控稻瘟病菌附着胞分化和发育的信号传递的分子机理.
基金supported by grants from Hong Kong RGC (GRF #473908 and #475009)National Natural Science Foundation of China (No. 81071634)
文摘Nasopharyngeal carcinoma(NPC) is a malignancy with remarkable ethnic and geographic distribution in southern China and Southeast Asia.Alternative to genetic changes,aberrant epigenetic events disrupt multiple genes involved in cell signaling pathways through DNA methylation of promoter CpG islands and/or histone modifications.These epigenetic alterations grant cell growth advantage and contribute to the initiation and progression of NPC.In this review,we summarize the epigenetic deregulation of cell signaling in NPC tumorigenesis and highlight the importance of identifying epigenetic cell signaling regulators in NPC research.Developing pharmacologic strategies to reverse the epigenetic-silencing of cell signaling regulators might thus be useful to NPC prevention and therapy.
基金supported in part by a grant from the National Institutes of Health (NIH), USA (R01CA201011 to BL)a grant from the National Natural Science Foundation of China (81472763 to BL)
文摘HER3 belongs to the human epidermal growth factor receptor(HER) family which also includes HER1/EGFR/erb B1,HER2/erb B2,and HER4/erb B4. As a unique member of the HER family,HER3 lacks or has little intrinsic tyrosine kinase activity. It frequently co-expresses and forms heterodimers with other receptor tyrosine kinases(RTKs) in cancer cells to activate oncogenic signaling,especially the PI-3 K/Akt pathway and Src kinase. Elevated expression of HER3 has been observed in a wide variety of human cancers and associates with a worse survival in cancer patients with solid tumors.Studies on the underlying mechanism implicate HER3 expression as a major cause of treatment failure in cancer therapy. Activation of HER3 signaling has also been shown to promote cancer metastasis. These data strongly support the notion that therapeutic inactivation of HER3 and/or its downstream signaling is required to overcome treatment resistance and improve the outcomes of cancer patients.