There is growing evidence that metabolic alterations play an important role in cancer development and progression.The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation.Elevated f...There is growing evidence that metabolic alterations play an important role in cancer development and progression.The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation.Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism.An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival,as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival.Based on the data that serum fatty acid synthase(FASN),also known as oncoantigen 519,is elevated in patients with certain types of cancer,its serum level was proposed as a marker of neoplasia.This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma(PDAC),the most common pancreatic neoplasm,characterized by high mortality.We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism.Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer.In particular,FASN is a viable candidate for indicator of pathologic state,marker of neoplasia,as well as,pharmacological treatment target in pancreatic cancer.Recent research showed that,in addition to lipogenesis,certain cancer cells can use fatty acids from circulation,derived from diet(chylomicrons),synthesized in liver,or released from adipose tissue for their growth.Thus,the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation.展开更多
Canola （Brassica napus L.） is one of the most important oilseed crops in the world and its seed yield and quality are significantly affected by drought stress. As an innate and adaptive response to water deficit, la...Canola （Brassica napus L.） is one of the most important oilseed crops in the world and its seed yield and quality are significantly affected by drought stress. As an innate and adaptive response to water deficit, land plants avoid potential damage by rapid biosynthesis of the phytohormone abscisic acid （ABA）, which triggers stomatal closure to reduce transpirational water loss. The ABA-mediated stomatal response is a dosage-dependent process; thus, one genetic engineering approach for achieving drought avoidance could be to sensitize the guard cell＇s responsiveness to this hormone. Recent genetic studies have pinpointed protein farnesyltransferase as a key negative regulator controlling ABA sensitivity in the guard cells. We have previously shown that down-regulation of the gene encoding Arabidopsis β-subunit of farnesyltransferase （ERA1） enhances the plant＇s sensitivity to ABA and drought tolerance. Although the β-subunit of famesyltransferase （AtFTA） is also implicated in ABA sensing, the effectiveness of using such a gene target for improving drought tolerance in a crop plant has not been validated. Here, we report the identification and characterization of the promoter of Arabidopsis hydroxypyruvate reductase （AtHPR1）, which expresses specifically in the shoot and not in non-photosynthetic tissues such as root. The promoter region of AtHPR1 contains the core motif of the well characterized dehydration-responsive cis-acting element and we have confirmed thatAtHPR1 expression is inducible by drought stress. Conditional and specific down-regulation of FTA in canola using the AtHPR1 promoter driving an RNAi construct resulted in yield protection against drought stress in the field. Using this molecular strategy, we have made significant progress in engineering drought tolerance in this important crop species.展开更多
Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol cond...Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol condensation,cyclization,DDQ dehydrogenation,regioselective demethylation,debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials.Among them,compounds 7―15 are new compounds.Natural products 2―4 were firstly total synthesized.The syntheses of compounds 1,5 and 6 were efficiently improved by the new synthetic routes.The structures of all synthetic compounds were confirmed by NMR,IR spectra and MS.展开更多
对于有丝分裂和减数分裂而言,着丝粒是不可或缺的重要功能元件。近几年的研究表明,着丝粒蛋白F(Centromere Protein F,CENPF)是细胞周期调控的关键蛋白。CENPF是一种分子量为367kDa的核定位蛋白,它在有丝分裂前期开始增加,在有丝分裂期...对于有丝分裂和减数分裂而言,着丝粒是不可或缺的重要功能元件。近几年的研究表明,着丝粒蛋白F(Centromere Protein F,CENPF)是细胞周期调控的关键蛋白。CENPF是一种分子量为367kDa的核定位蛋白,它在有丝分裂前期开始增加,在有丝分裂期定位于动粒,末期开始迅速降解。CENPF缺失会造成有丝分裂缺陷,包括纺锤体无法正常组装、染色体非正常排列和分离,甚至细胞死亡。同时,CENPF可能与纺锤体组装检验点(Spindle Assembly Checkpoint,SAC)的活性有关。CENPF功能的发挥取决于法尼基化修饰,CENPF的过表达则可能导致肿瘤的发生,通过法尼基转移酶抑制剂(Farnesyltransferase Inhibitor,FTI)处理细胞则会抑制肿瘤细胞的增殖。同时,CENPF对小鼠早期胚胎的发育也具有重要的调控作用。对近些年CENPF的研究进展进行了综述,并提出了尚待解决的关键问题,希望可以为后续的研究提供一些思路。展开更多
Artemisinin is a novel effective antimalarial drug extracted from the medicinal plant Artemisia annua L. Owing to the tight market and low yield of artemisinin, there is great interest in enhancing the production of a...Artemisinin is a novel effective antimalarial drug extracted from the medicinal plant Artemisia annua L. Owing to the tight market and low yield of artemisinin, there is great interest in enhancing the production of artemisinin. In the present study, farnesyi diphosphate synthase （FPS） was overexpressed in high-yield A. annua to Increase the artemisinin content. The FPS activity in transgenic A. ennue was twoto threefold greater than that In non-transgenic A. annua. The highest artemisinin content in transgenic A. annua was approximately 0.9% （dry weight）, which was 34.4% higher than that in non-transgenic A. annua. The results demonstrate the regulatory role of FPS in artemisinin biosynthesis.展开更多
Background Genetic factors are important in the pathogenesis of osteoporosis,but less is known about the genetic determinants of osteoporosis treatment.We aimed to explore the association between the gene polymorphism...Background Genetic factors are important in the pathogenesis of osteoporosis,but less is known about the genetic determinants of osteoporosis treatment.We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase （FDPS） in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.Methods The study group comprised 639 postmenopausal women aged （62.2＆#177;7.0） years with osteoporosis or osteopenia who had been randomly assigned to low dose group （70 mg/2w） or standard dose group （70 mg/w） of alendronate in this 1-year study.We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul.Before and after treatment,serum levels of calcium,phosphate,alkaline phosphatase （ALP）,cross linked C-telopeptide of type Ⅰ collagen （β-CTX） were detected.Bone mineral density （BMD） at lumbar spine and proximal femur was measured.The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD,bone turnover biomarkers after the treatment.Results The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck,and patients with CC genotype had significantly higher baseline femoral neck BMD （（733.6＆#177;84.1） mg/cm2） than those with AC genotypes （（703.0＆#177;86.9） mg/cm2） and AA genotypes （（649.8＆#177;62.4） mg/cm2） （P 〈0.01）.No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS.The percentage change of serum ALP level was significantly lower in patients with CC genotype （-22.9%） than that in those with AC genotype （-24.1%） and AA genotype （-29.8%） of FDPS after 12 months of alendronate treatment （P 〈0.05）.Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.Conclusions FDPS gene was probably a candidate gene to predict femoral neck BMD at basel展开更多
Farnesyl dlphosphate synthase （FPS; EC 2.5.1.10） catalyzes the production of 15-carbon farnesyl dlphosphate which Is a branch-point Intermediate for many terpenoids. This reaction Is considered to be a ratelimiting ...Farnesyl dlphosphate synthase （FPS; EC 2.5.1.10） catalyzes the production of 15-carbon farnesyl dlphosphate which Is a branch-point Intermediate for many terpenoids. This reaction Is considered to be a ratelimiting step In terpenold biosynthesis. Here we report for the first time the cloning of a new full-length cDNA encoding farnesyl dlphosphate synthase from a gymnosperm plant species, Taxus media Rehder, designated as TmFPS1. The full-length cDNA of TmFPS1 （GenBank accession number： AY461811） was 1 464 bp with a 1 056-bp open reading frame encoding a 351-amino acid polypeptlde with a calculated molecular weight of 40.3 kDa and a theoretical pl of 5.07. Biolnformatlc analysis revealed that TmFPS1 contained all five conserved domains of prenyltransferases, and showed homology to other FPSs of plant origin. Phylogenetlc analysis showed that farnesyl dlphosphate synthases can be divided Into two groups： one of prokaryotic origin and the other of eukaryotic origin. TmFPS1 was grouped with FPSs of plant origin. Homologybased structural modeling showed that TmFPS1 had the typical spatial structure of FPS, whose most prominent structural feature Is the arrangement of 13 core helices around a large central cavity In which the catalytic reaction takes place. Our blolnformatic analysis strongly suggests that TmFPS1 is a functional gene. Southern blot analysis revealed that TmFPS1 belongs to a small FPSgene family in T. media. Northern blot analysis indicated that TmFPS1 is expressed in all tested tissues, Including the needles, stems and roots of T. media. Subsequently, functional complementatlon with TmFPS1 in a FPS-deflclent mutant yeast demonstrated that TmFPS1 did encode farnesyl dlphosphate synthase, which rescued the yeast mutant. This study will be helpful In future Investigations aiming at understanding the detailed role of FPS In terpenold biosynthesis flux control at the molecular genetic level.展开更多
The study aims to reveal phylogenetic and evolutionary relationship between aerobic anoxygenic phototrophic bacteria（AAnPB） and their relatives,anaerobic anoxygenic phototrophic bacteria（AnAnPB） and nonphototrophi...The study aims to reveal phylogenetic and evolutionary relationship between aerobic anoxygenic phototrophic bacteria（AAnPB） and their relatives,anaerobic anoxygenic phototrophic bacteria（AnAnPB） and nonphototrophic bacteria（NPB,which had high homology of 16S rDNA gene with AAnPB and fell into the same genus）,and validate reliability and usefulness of farnesyl pyrophosphate synthase（FPPS） gene for the phylogenetic determination.FPPS genes with our modified primers and 16S rDNA genes with general primers,were amplified and sequenced or retrieved from GenBank database.In contrast to 16S rDNA gene phylogenetic tree,AAnPB were grouped into two clusters and one branch alone with no intermingling with NPB and AnAnPB in the tree constructed on FPPS.One branch of AAnPB,in both trees,was located closer to outgroup species than AnAnPB,which implicated that some AAnPB would be diverged earlier in FPPS evolutionary history than AnAnPB and NPB.Some AAnPB and NPB were closer located in both trees and this suggested that they were the closer relatives than AnAnPB.Combination codon usage in FPPS with phylogenetic analysis,the results indicates that FPPS gene and 16S rRNA gene have similar evolutionary pattern but the former seems to be more reliable and useful in determining the phylogenic and evolutionary relationship between AAnPB and their relatives.This is the first attempt to use a molecular marker beside 16S rRNA gene for studying the phylogeny of AAnPB,and the study may also be helpful in understanding the evolutionary relationship among phototrophic microbes and the trends of photosynthetic genes transfer.展开更多
The monoterpene d limonene inhibit the plasma membrane associated P21 ras expression and the posttranslational isoprenylation of P21 ras , a mechanism that may contribute to its efficacy in the chemoprevent...The monoterpene d limonene inhibit the plasma membrane associated P21 ras expression and the posttranslational isoprenylation of P21 ras , a mechanism that may contribute to its efficacy in the chemoprevention and therapy of chemically induced rodent cancers and some human solid tumor cells. In the present study,the relative abilities of d limonene to inhibit membrane associated P21 ras expression in pancreas tumor cell(PaCa) was carried out with Western blotting, and the inhibition of farnesyl protein transferase (FTPase) activity during the Ras protein isoprenylation and cell proliferation were determined.Concomitantly,the effects of d limonene on P21 ras localization by immunohistochemistry and H ras oncogene expression in PaCa tumor cell line by Northern blotting were observed. The results showed that d limonene inhibited FPTase activity, thus to reduce P21H ras isoprenylation. d limonene could decrease P21 ras membrane association and increase cytosolic accumulation of P21 ras . This phenomenon was also noted when d limonene treated PaCa cells were stained immunohistochemically with anti P21 ras antibody. It is suggested that the inhibition of FPTase activity was closely related with the inhibiton of P21 ras membrane association and the alteration of P21 ras localization. Inhibition of farnesylation of P21 ras altered their intracellular localization and, hence, disrupted their biological activity,but no relationship with H ras oncogene expression was found.展开更多
Farnesyl caffeate, synthesis of propolis and polar bud excretion, has been reported to exhibit anti-allergic effects in mice. However, little is known about anti-tumor effects. In this study, we investigated the effec...Farnesyl caffeate, synthesis of propolis and polar bud excretion, has been reported to exhibit anti-allergic effects in mice. However, little is known about anti-tumor effects. In this study, we investigated the effect of Farnesyl caffeate in cell proliferation of lung carcinoma cell line (H157). Antiproliferative effect and apoptosis on H157 cell were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT) and DNA fragmentation assay, respectively. Farnesyl caffeate inhibited the growth of H157 cell in dose-dependent manner. Morphological changes of nuclei by staining Hoechst 33258 and DNA fragmentation suggested that Farnesyl caffeate induced death involved in a mechanism of apoptosis. Moreover, caspase-3, caspase-7 and caspase-9 were activated by Farnesyl caffeate on H157 cell. The protein expressions of Bax and Bcl-2 were down-regulated by Farnesyl caffeate, resulting in cytochrome c release from the mitochondria. Farnesyl caffeate significantly increased the expression of p53 proteins which indicates that p53 plays a pivotal role in the initiation phase of Farnesyl caffeate-induced HepG2 cell apoptosis. These results demonstrated Farnesyl caffeate-induced apoptosis in human lung carcinoma cell line. More detailed mechanism of ?Farnesyl caffeate-induced H157 apoptosis remains to be elucidated.展开更多
Sesquiterpenoids play an import role in the direct or indirect defense of plants.Farnesyl pyrophosphate synthases(FPSs)catalyze the biosynthesis of farnesyl pyrophosphate,which is a key precursor of farnesol and(E)-β...Sesquiterpenoids play an import role in the direct or indirect defense of plants.Farnesyl pyrophosphate synthases(FPSs)catalyze the biosynthesis of farnesyl pyrophosphate,which is a key precursor of farnesol and(E)-β-farnesene.In the current study,two FPS genes in Gossypium hirsutum,GhFPS1 and GhFPS2,were heterologously cloned and functionally characterized in a greenhouse setting.The open reading frames for full-length GhFPS1 and GhFPS2 were each 1029 nucleotides,and encoded two proteins of 342 amino acids with molecular weights of 39.4 kDa.The deduced amino acid sequences of GhFPS1–2 showed high identity to FPSs of other plants.Quantitative real-time PCR analysis revealed that GhFPS1 and GhFPS2 were highly expressed in G.hirsutum leaves,and were upregulated in methyl jasmonate(MeJA)-,methyl salicylate(MeSA)-and aphid infestation-treated cotton plants.The recombinant proteins of either GhFPS1 or GhFPS2 plus calf intestinal alkaline phosphatase could convert geranyl diphosphate(GPP)or isopentenyl diphosphate(IPP)to one major product,farnesol.Moreover,in electrophysiological response and Y-tube olfactometer assays,farnesol showed obvious attractiveness to female Aphidius gifuensis,which is an important parasitic wasp of aphids.Our findings suggest that two GhFPSs are involved in farnesol biosynthesis and they play a crucial role in indirect defense of cotton against aphid infestation.展开更多
All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecul...All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecular patterns(DAMPs).In addition to well‐characterized DAMPs such as high‐mobility group box 1 and adenosine triphosphate,studies on new classes of DAMPs have emerged.Here,we review recent reports of a new class of isoprenoid‐derived DAMPs,including farnesyl pyrophosphate and geranylgeranyl pyrophosphate,both of which are pivotal metabolic inter-mediates of the mevalonate pathway.We also explore the roles of old and new DAMPs in autoimmune diseases that result from dysregulated inflammation.The findings highlight that understanding the functional mechanisms of DAMPs is important to enrich the DAMP family and decipher their immunoregulatory mechanisms to provide new therapeutics for the prevention and treatment of autoimmune diseases.展开更多
基金Supported by Medical University of Gdansk Grants ST-41,ST-40
文摘There is growing evidence that metabolic alterations play an important role in cancer development and progression.The metabolism of cancer cells is reprogrammed in order to support their rapid proliferation.Elevated fatty acid synthesis is one of the most important aberrations of cancer cell metabolism.An enhancement of fatty acids synthesis is required both for carcinogenesis and cancer cell survival,as inhibition of key lipogenic enzymes slows down the growth of tumor cells and impairs their survival.Based on the data that serum fatty acid synthase(FASN),also known as oncoantigen 519,is elevated in patients with certain types of cancer,its serum level was proposed as a marker of neoplasia.This review aims to demonstrate the changes in lipid metabolism and other metabolic processes associated with lipid metabolism in pancreatic ductal adenocarcinoma(PDAC),the most common pancreatic neoplasm,characterized by high mortality.We also addressed the influence of some oncogenic factors and tumor suppressors on pancreatic cancer cell metabolism.Additionally the review discusses the potential role of elevated lipid synthesis in diagnosis and treatment of pancreatic cancer.In particular,FASN is a viable candidate for indicator of pathologic state,marker of neoplasia,as well as,pharmacological treatment target in pancreatic cancer.Recent research showed that,in addition to lipogenesis,certain cancer cells can use fatty acids from circulation,derived from diet(chylomicrons),synthesized in liver,or released from adipose tissue for their growth.Thus,the interactions between de novo lipogenesis and uptake of fatty acids from circulation by PDAC cells require further investigation.
文摘Canola （Brassica napus L.） is one of the most important oilseed crops in the world and its seed yield and quality are significantly affected by drought stress. As an innate and adaptive response to water deficit, land plants avoid potential damage by rapid biosynthesis of the phytohormone abscisic acid （ABA）, which triggers stomatal closure to reduce transpirational water loss. The ABA-mediated stomatal response is a dosage-dependent process; thus, one genetic engineering approach for achieving drought avoidance could be to sensitize the guard cell＇s responsiveness to this hormone. Recent genetic studies have pinpointed protein farnesyltransferase as a key negative regulator controlling ABA sensitivity in the guard cells. We have previously shown that down-regulation of the gene encoding Arabidopsis β-subunit of farnesyltransferase （ERA1） enhances the plant＇s sensitivity to ABA and drought tolerance. Although the β-subunit of famesyltransferase （AtFTA） is also implicated in ABA sensing, the effectiveness of using such a gene target for improving drought tolerance in a crop plant has not been validated. Here, we report the identification and characterization of the promoter of Arabidopsis hydroxypyruvate reductase （AtHPR1）, which expresses specifically in the shoot and not in non-photosynthetic tissues such as root. The promoter region of AtHPR1 contains the core motif of the well characterized dehydration-responsive cis-acting element and we have confirmed thatAtHPR1 expression is inducible by drought stress. Conditional and specific down-regulation of FTA in canola using the AtHPR1 promoter driving an RNAi construct resulted in yield protection against drought stress in the field. Using this molecular strategy, we have made significant progress in engineering drought tolerance in this important crop species.
基金Supported by the Science & Technology Planning Project of Hunan Province,China (No.2011FJ3214)
文摘Bioactive natural polymethoxyflavones 1―6 and their vinyl ether derivatives 7―15 were synthesized by bromination,aromatic nucleophilic substitution,methylation,benzyl protection,Friedel-Crafts acetylation,aldol condensation,cyclization,DDQ dehydrogenation,regioselective demethylation,debenzylation and O-prenylation or O-farnesylation with resorcinol and appropriate substituted benzaldehydes as starting materials.Among them,compounds 7―15 are new compounds.Natural products 2―4 were firstly total synthesized.The syntheses of compounds 1,5 and 6 were efficiently improved by the new synthetic routes.The structures of all synthetic compounds were confirmed by NMR,IR spectra and MS.
基金the National Natural Science Foundation of China （30171142）.
文摘Artemisinin is a novel effective antimalarial drug extracted from the medicinal plant Artemisia annua L. Owing to the tight market and low yield of artemisinin, there is great interest in enhancing the production of artemisinin. In the present study, farnesyi diphosphate synthase （FPS） was overexpressed in high-yield A. annua to Increase the artemisinin content. The FPS activity in transgenic A. ennue was twoto threefold greater than that In non-transgenic A. annua. The highest artemisinin content in transgenic A. annua was approximately 0.9% （dry weight）, which was 34.4% higher than that in non-transgenic A. annua. The results demonstrate the regulatory role of FPS in artemisinin biosynthesis.
基金grants from the National Natural Science Foundation of China，National Key Program of Clinical Science
文摘Background Genetic factors are important in the pathogenesis of osteoporosis,but less is known about the genetic determinants of osteoporosis treatment.We aimed to explore the association between the gene polymorphisms of key enzyme farnesyl diphosphate synthase （FDPS） in mevalonate signaling pathway of osteoclast and response to alendronate therapy in osteoporotic postmenopausal women in China.Methods The study group comprised 639 postmenopausal women aged （62.2＆#177;7.0） years with osteoporosis or osteopenia who had been randomly assigned to low dose group （70 mg/2w） or standard dose group （70 mg/w） of alendronate in this 1-year study.We identified allelic variant of the FDPS gene using the polymerase chain reaction and restriction enzyme Faul.Before and after treatment,serum levels of calcium,phosphate,alkaline phosphatase （ALP）,cross linked C-telopeptide of type Ⅰ collagen （β-CTX） were detected.Bone mineral density （BMD） at lumbar spine and proximal femur was measured.The association was analyzed between the polymorphisms of FDPS gene and the changes of BMD,bone turnover biomarkers after the treatment.Results The FDPS rs2297480 polymorphisms were associated with baseline BMD at femoral neck,and patients with CC genotype had significantly higher baseline femoral neck BMD （（733.6＆#177;84.1） mg/cm2） than those with AC genotypes （（703.0＆#177;86.9） mg/cm2） and AA genotypes （（649.8＆#177;62.4） mg/cm2） （P 〈0.01）.No significant difference in BMD at lumbar spine was observed among different genotypes of FDPS.The percentage change of serum ALP level was significantly lower in patients with CC genotype （-22.9%） than that in those with AC genotype （-24.1%） and AA genotype （-29.8%） of FDPS after 12 months of alendronate treatment （P 〈0.05）.Neither percentage change of BMD nor β-CTX level after alendronate treatment had association with FDPS genotype.Conclusions FDPS gene was probably a candidate gene to predict femoral neck BMD at basel
基金Supported by the Hi-Tech Research and Development(863) Program of China,and the National Natural Science Foundation of China(30500303)
文摘Farnesyl dlphosphate synthase （FPS; EC 2.5.1.10） catalyzes the production of 15-carbon farnesyl dlphosphate which Is a branch-point Intermediate for many terpenoids. This reaction Is considered to be a ratelimiting step In terpenold biosynthesis. Here we report for the first time the cloning of a new full-length cDNA encoding farnesyl dlphosphate synthase from a gymnosperm plant species, Taxus media Rehder, designated as TmFPS1. The full-length cDNA of TmFPS1 （GenBank accession number： AY461811） was 1 464 bp with a 1 056-bp open reading frame encoding a 351-amino acid polypeptlde with a calculated molecular weight of 40.3 kDa and a theoretical pl of 5.07. Biolnformatlc analysis revealed that TmFPS1 contained all five conserved domains of prenyltransferases, and showed homology to other FPSs of plant origin. Phylogenetlc analysis showed that farnesyl dlphosphate synthases can be divided Into two groups： one of prokaryotic origin and the other of eukaryotic origin. TmFPS1 was grouped with FPSs of plant origin. Homologybased structural modeling showed that TmFPS1 had the typical spatial structure of FPS, whose most prominent structural feature Is the arrangement of 13 core helices around a large central cavity In which the catalytic reaction takes place. Our blolnformatic analysis strongly suggests that TmFPS1 is a functional gene. Southern blot analysis revealed that TmFPS1 belongs to a small FPSgene family in T. media. Northern blot analysis indicated that TmFPS1 is expressed in all tested tissues, Including the needles, stems and roots of T. media. Subsequently, functional complementatlon with TmFPS1 in a FPS-deflclent mutant yeast demonstrated that TmFPS1 did encode farnesyl dlphosphate synthase, which rescued the yeast mutant. This study will be helpful In future Investigations aiming at understanding the detailed role of FPS In terpenold biosynthesis flux control at the molecular genetic level.
基金The National Natural Science Foundation of China under contract Nos 40232021 and 40576063
文摘The study aims to reveal phylogenetic and evolutionary relationship between aerobic anoxygenic phototrophic bacteria（AAnPB） and their relatives,anaerobic anoxygenic phototrophic bacteria（AnAnPB） and nonphototrophic bacteria（NPB,which had high homology of 16S rDNA gene with AAnPB and fell into the same genus）,and validate reliability and usefulness of farnesyl pyrophosphate synthase（FPPS） gene for the phylogenetic determination.FPPS genes with our modified primers and 16S rDNA genes with general primers,were amplified and sequenced or retrieved from GenBank database.In contrast to 16S rDNA gene phylogenetic tree,AAnPB were grouped into two clusters and one branch alone with no intermingling with NPB and AnAnPB in the tree constructed on FPPS.One branch of AAnPB,in both trees,was located closer to outgroup species than AnAnPB,which implicated that some AAnPB would be diverged earlier in FPPS evolutionary history than AnAnPB and NPB.Some AAnPB and NPB were closer located in both trees and this suggested that they were the closer relatives than AnAnPB.Combination codon usage in FPPS with phylogenetic analysis,the results indicates that FPPS gene and 16S rRNA gene have similar evolutionary pattern but the former seems to be more reliable and useful in determining the phylogenic and evolutionary relationship between AAnPB and their relatives.This is the first attempt to use a molecular marker beside 16S rRNA gene for studying the phylogeny of AAnPB,and the study may also be helpful in understanding the evolutionary relationship among phototrophic microbes and the trends of photosynthetic genes transfer.
文摘The monoterpene d limonene inhibit the plasma membrane associated P21 ras expression and the posttranslational isoprenylation of P21 ras , a mechanism that may contribute to its efficacy in the chemoprevention and therapy of chemically induced rodent cancers and some human solid tumor cells. In the present study,the relative abilities of d limonene to inhibit membrane associated P21 ras expression in pancreas tumor cell(PaCa) was carried out with Western blotting, and the inhibition of farnesyl protein transferase (FTPase) activity during the Ras protein isoprenylation and cell proliferation were determined.Concomitantly,the effects of d limonene on P21 ras localization by immunohistochemistry and H ras oncogene expression in PaCa tumor cell line by Northern blotting were observed. The results showed that d limonene inhibited FPTase activity, thus to reduce P21H ras isoprenylation. d limonene could decrease P21 ras membrane association and increase cytosolic accumulation of P21 ras . This phenomenon was also noted when d limonene treated PaCa cells were stained immunohistochemically with anti P21 ras antibody. It is suggested that the inhibition of FPTase activity was closely related with the inhibiton of P21 ras membrane association and the alteration of P21 ras localization. Inhibition of farnesylation of P21 ras altered their intracellular localization and, hence, disrupted their biological activity,but no relationship with H ras oncogene expression was found.
文摘Farnesyl caffeate, synthesis of propolis and polar bud excretion, has been reported to exhibit anti-allergic effects in mice. However, little is known about anti-tumor effects. In this study, we investigated the effect of Farnesyl caffeate in cell proliferation of lung carcinoma cell line (H157). Antiproliferative effect and apoptosis on H157 cell were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay (MTT) and DNA fragmentation assay, respectively. Farnesyl caffeate inhibited the growth of H157 cell in dose-dependent manner. Morphological changes of nuclei by staining Hoechst 33258 and DNA fragmentation suggested that Farnesyl caffeate induced death involved in a mechanism of apoptosis. Moreover, caspase-3, caspase-7 and caspase-9 were activated by Farnesyl caffeate on H157 cell. The protein expressions of Bax and Bcl-2 were down-regulated by Farnesyl caffeate, resulting in cytochrome c release from the mitochondria. Farnesyl caffeate significantly increased the expression of p53 proteins which indicates that p53 plays a pivotal role in the initiation phase of Farnesyl caffeate-induced HepG2 cell apoptosis. These results demonstrated Farnesyl caffeate-induced apoptosis in human lung carcinoma cell line. More detailed mechanism of ?Farnesyl caffeate-induced H157 apoptosis remains to be elucidated.
基金This work was supported by the National Natural Science Foundation of China(31772176,31672038 and 31621064)and the National Key Research and Development Program of China(2017YFDO201900 and 2017YFD0200400).
文摘Sesquiterpenoids play an import role in the direct or indirect defense of plants.Farnesyl pyrophosphate synthases(FPSs)catalyze the biosynthesis of farnesyl pyrophosphate,which is a key precursor of farnesol and(E)-β-farnesene.In the current study,two FPS genes in Gossypium hirsutum,GhFPS1 and GhFPS2,were heterologously cloned and functionally characterized in a greenhouse setting.The open reading frames for full-length GhFPS1 and GhFPS2 were each 1029 nucleotides,and encoded two proteins of 342 amino acids with molecular weights of 39.4 kDa.The deduced amino acid sequences of GhFPS1–2 showed high identity to FPSs of other plants.Quantitative real-time PCR analysis revealed that GhFPS1 and GhFPS2 were highly expressed in G.hirsutum leaves,and were upregulated in methyl jasmonate(MeJA)-,methyl salicylate(MeSA)-and aphid infestation-treated cotton plants.The recombinant proteins of either GhFPS1 or GhFPS2 plus calf intestinal alkaline phosphatase could convert geranyl diphosphate(GPP)or isopentenyl diphosphate(IPP)to one major product,farnesol.Moreover,in electrophysiological response and Y-tube olfactometer assays,farnesol showed obvious attractiveness to female Aphidius gifuensis,which is an important parasitic wasp of aphids.Our findings suggest that two GhFPSs are involved in farnesol biosynthesis and they play a crucial role in indirect defense of cotton against aphid infestation.
基金The authors acknowledge support from the Tsinghua University Spring Breeze Fund,Center for Life Sciences,and Institute for Immunology,Tsinghua University,and grants from the Ministry of Science and Technology of China(2021YFC2300500 and 2021YFC2302403)National Natural Science Foundation of China(32141004,81825010,81730043,and 81621002).
文摘All organisms living in complex environments have evolved effective mechanisms of dynamic responses to extracellular stimuli.The immune system activates when damaged or injured cells release damage‐associated molecular patterns(DAMPs).In addition to well‐characterized DAMPs such as high‐mobility group box 1 and adenosine triphosphate,studies on new classes of DAMPs have emerged.Here,we review recent reports of a new class of isoprenoid‐derived DAMPs,including farnesyl pyrophosphate and geranylgeranyl pyrophosphate,both of which are pivotal metabolic inter-mediates of the mevalonate pathway.We also explore the roles of old and new DAMPs in autoimmune diseases that result from dysregulated inflammation.The findings highlight that understanding the functional mechanisms of DAMPs is important to enrich the DAMP family and decipher their immunoregulatory mechanisms to provide new therapeutics for the prevention and treatment of autoimmune diseases.
