Auxin influences a variety of developmental and physiological processes. Early reports, suggested that auxin might affect plant stress response. We have identified a number of auxin responsive genes in Arabidopsis tha...Auxin influences a variety of developmental and physiological processes. Early reports, suggested that auxin might affect plant stress response. We have identified a number of auxin responsive genes in Arabidopsis thaliana (L.) Heynh. by using cDNA an-ay and found that stress responsive genes, such as,Arabidopsis homolog of MEK kinase 1 (ATMEKK1), ReL/SpoT homolog 3 ( At-RSH3), Catalase 1 ( Cat1) and Ferritin 1 (Fer1), were down-regulated by auxin, indicating that auxin regulates ale expression of stress responsive genes. We also demonstrated that nitrilase genes, nitrilase I ( NIT]) and nitrilase 2 (NIT2) involving in indole-3-acetic acid (IAA) biosynthesis, were induced by salinity stress, suggesting that the level of IAA might increase in response to salinity stress. To dissect the signal pathway involved in the interaction, two auxin insensitive mutants, auxin resistant 2 (axr2) and auxin resistant 1-3 (axrl-3) were used. Stress responsive genes were induced by salt stress in wild type and axr2, but not in axr1-3. The result suggests that die interaction between auxin and stress responses may be linked in the ubiquitin pathway.展开更多
AIM： To examine the underlying mechanisms of erlotinib-induced growth inhibition in hepatocellular carcinoma （HCC）. METHODS： Erlotinib-induced alterations in gene expression were evaluated using cDNA array technol...AIM： To examine the underlying mechanisms of erlotinib-induced growth inhibition in hepatocellular carcinoma （HCC）. METHODS： Erlotinib-induced alterations in gene expression were evaluated using cDNA array technology; changes in protein expression and/or protein activation due to erlotinib treatment as well as IGF-1-induced EGFR transactivation were investigated using Western blotting. RESULTS： Erlotinib treatment inhibited the mitogen activated protein （MAP）-kinase pathway and signal transducer of activation and transcription （STAT）- mediated signaling which led to an altered expression of apoptosis and cell cycle regulating genes as demonstrated by cDNA array technology. Overexpression of proapoptotic factors like caspases and gadds associated with a down-regulation of antiapoptotic factors like Bcl-2, Bcl-XL or jun D accounted for erlotinib＇s potency to induce apoptosis. Downregulation of cell cycle regulators promoting the G1/S-transition and overexpression of cyclin-dependent kinase inhibitors and gadds contributed to the induction of a G1/G0-arrest in response to erlotinib. Furthermore, we displayed the transactivation of EGFR-mediated signaling by the IGF-1-receptor and showed erlotinib＇s inhibitory effects on the receptor-receptor cross talk. CONCLUSION： Our study sheds light on the understanding of the mechanisms of action of EGFR-TK- inhibition in HCC-cells and thus might facilitate the design of combination therapies that act additively or synergistically. Moreover, our data on the pathways responding to erlotinib treatment could be helpful in predicting the responsiveness of tumors to EGFR-TKIs in the future.展开更多
Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are re...Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are responsible for the regulation of pluripotency and differentiation.During embryonic development,these pathways govern cell fate specifications as well as the formation of tissues and organs.In adulthood,their normal functions are important for tissue homeostasis and regeneration,whereas aberrations result in diseases,such as cancer and degenerative disorders.In complex biological systems,stem cell signaling pathways work in concert as a network and exhibit crosstalk,such as the negative crosstalk between Wnt and Notch.Over the past decade,genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways.Indeed,discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry.Remarkable progress has been made and several promising drug candidates have entered into clinical trials.This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.展开更多
文摘Auxin influences a variety of developmental and physiological processes. Early reports, suggested that auxin might affect plant stress response. We have identified a number of auxin responsive genes in Arabidopsis thaliana (L.) Heynh. by using cDNA an-ay and found that stress responsive genes, such as,Arabidopsis homolog of MEK kinase 1 (ATMEKK1), ReL/SpoT homolog 3 ( At-RSH3), Catalase 1 ( Cat1) and Ferritin 1 (Fer1), were down-regulated by auxin, indicating that auxin regulates ale expression of stress responsive genes. We also demonstrated that nitrilase genes, nitrilase I ( NIT]) and nitrilase 2 (NIT2) involving in indole-3-acetic acid (IAA) biosynthesis, were induced by salinity stress, suggesting that the level of IAA might increase in response to salinity stress. To dissect the signal pathway involved in the interaction, two auxin insensitive mutants, auxin resistant 2 (axr2) and auxin resistant 1-3 (axrl-3) were used. Stress responsive genes were induced by salt stress in wild type and axr2, but not in axr1-3. The result suggests that die interaction between auxin and stress responses may be linked in the ubiquitin pathway.
基金Supported by Deutsche Forschungsgemeinschaft (DFG),Deutsche Krebshilfe and Sonnenfeld-Stiftung Berlin
文摘AIM： To examine the underlying mechanisms of erlotinib-induced growth inhibition in hepatocellular carcinoma （HCC）. METHODS： Erlotinib-induced alterations in gene expression were evaluated using cDNA array technology; changes in protein expression and/or protein activation due to erlotinib treatment as well as IGF-1-induced EGFR transactivation were investigated using Western blotting. RESULTS： Erlotinib treatment inhibited the mitogen activated protein （MAP）-kinase pathway and signal transducer of activation and transcription （STAT）- mediated signaling which led to an altered expression of apoptosis and cell cycle regulating genes as demonstrated by cDNA array technology. Overexpression of proapoptotic factors like caspases and gadds associated with a down-regulation of antiapoptotic factors like Bcl-2, Bcl-XL or jun D accounted for erlotinib＇s potency to induce apoptosis. Downregulation of cell cycle regulators promoting the G1/S-transition and overexpression of cyclin-dependent kinase inhibitors and gadds contributed to the induction of a G1/G0-arrest in response to erlotinib. Furthermore, we displayed the transactivation of EGFR-mediated signaling by the IGF-1-receptor and showed erlotinib＇s inhibitory effects on the receptor-receptor cross talk. CONCLUSION： Our study sheds light on the understanding of the mechanisms of action of EGFR-TK- inhibition in HCC-cells and thus might facilitate the design of combination therapies that act additively or synergistically. Moreover, our data on the pathways responding to erlotinib treatment could be helpful in predicting the responsiveness of tumors to EGFR-TKIs in the future.
文摘Signaling pathways transduce extracellular stimuli into cells through molecular cascades to regulate cellular functions.In stem cells,a small number of pathways,notably those of TGF-?/BMP,Hedgehog,Notch,and Wnt,are responsible for the regulation of pluripotency and differentiation.During embryonic development,these pathways govern cell fate specifications as well as the formation of tissues and organs.In adulthood,their normal functions are important for tissue homeostasis and regeneration,whereas aberrations result in diseases,such as cancer and degenerative disorders.In complex biological systems,stem cell signaling pathways work in concert as a network and exhibit crosstalk,such as the negative crosstalk between Wnt and Notch.Over the past decade,genetic and genomic studies have identified a number of potential drug targets that are involved in stem cell signaling pathways.Indeed,discovery of new targets and drugs for these pathways has become one of the most active areas in both the research community and pharmaceutical industry.Remarkable progress has been made and several promising drug candidates have entered into clinical trials.This review focuses on recent advances in the discovery of novel drugs which target the Notch and Wnt pathways.
