SWEET transporters play a pivotal role in sugar transport in plants.However,their functions in pollen tube growth,especially in coniferous species remain unknown.Here,we used RT-qPCR to reveal that a SWEET1 gene was s...SWEET transporters play a pivotal role in sugar transport in plants.However,their functions in pollen tube growth,especially in coniferous species remain unknown.Here,we used RT-qPCR to reveal that a SWEET1 gene was specifically expressed in pollen and pollen tubes of Picea wilsonii.A pollen germination assay showed that PwSWEET1 was induced by H3BO3 but not by Ca^2+.In a sugar specificity experiment,sucrose(Suc)and glucose(Glc)were effective sugars for pollen germination and pollen tube growth.PwSWEET1 expression was induced most by Suc and Glc.Heterologous expression of PwSWEET1 in yeast showed that PwSWEET1 can restore the glucose absorption in yeast strain EBY.VW4000,which has a hexose absorption defect,and the absorption of glucose is pH-independent.This evidence supports the involvment of PwSWEET1 in boron-dependent glucose transport in pollen germination and pollen tube growth of Picea wilsonii.展开更多
Although NPM1 mutations are frequently found in acute myeloid leukemia patients,therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy.Here we demonstrated that heliangin...Although NPM1 mutations are frequently found in acute myeloid leukemia patients,therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy.Here we demonstrated that heliangin,a natural sesquiterpene lactone,exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells,with no apparent toxicity to normal hematogenous cells,by inhibiting their proliferation,inducing apoptosis,causing cell cycle arrest,and promoting differentiation.In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2(RPS2)is the main target of heliangin in treating NPM1 mutant AML.Upon covalent binding to the C222 site of RPS2,the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes,leading to nucleolar stress,which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53.Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation,leading to a poor prognosis.We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target.Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients,especially those with NPM1 mutations.展开更多
基金This work was supported by the grant from Agricultural Ministry of China(No.2016ZX08009-003-002).
文摘SWEET transporters play a pivotal role in sugar transport in plants.However,their functions in pollen tube growth,especially in coniferous species remain unknown.Here,we used RT-qPCR to reveal that a SWEET1 gene was specifically expressed in pollen and pollen tubes of Picea wilsonii.A pollen germination assay showed that PwSWEET1 was induced by H3BO3 but not by Ca^2+.In a sugar specificity experiment,sucrose(Suc)and glucose(Glc)were effective sugars for pollen germination and pollen tube growth.PwSWEET1 expression was induced most by Suc and Glc.Heterologous expression of PwSWEET1 in yeast showed that PwSWEET1 can restore the glucose absorption in yeast strain EBY.VW4000,which has a hexose absorption defect,and the absorption of glucose is pH-independent.This evidence supports the involvment of PwSWEET1 in boron-dependent glucose transport in pollen germination and pollen tube growth of Picea wilsonii.
基金supported by grants from the National Natural Science Foundation of China(82074067)Natural Science Foundation of Jiangsu Province China(BK20181419,China)Natural Foundation of Jiangsu Higher Education Institutions of China(19KJA310006)。
文摘Although NPM1 mutations are frequently found in acute myeloid leukemia patients,therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy.Here we demonstrated that heliangin,a natural sesquiterpene lactone,exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells,with no apparent toxicity to normal hematogenous cells,by inhibiting their proliferation,inducing apoptosis,causing cell cycle arrest,and promoting differentiation.In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2(RPS2)is the main target of heliangin in treating NPM1 mutant AML.Upon covalent binding to the C222 site of RPS2,the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes,leading to nucleolar stress,which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53.Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation,leading to a poor prognosis.We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target.Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients,especially those with NPM1 mutations.