Objective To explore the role and mechanism of palmitoyltransferase DHHC7 in colorectal cancer invasiveness.Methods Colorectacl ancer cell lines HCT116 with ZDHHC7 knocked out were the knockout group,and wild-type HCT...Objective To explore the role and mechanism of palmitoyltransferase DHHC7 in colorectal cancer invasiveness.Methods Colorectacl ancer cell lines HCT116 with ZDHHC7 knocked out were the knockout group,and wild-type HCT116 cells were the control group.The mRNA expression of the two groupsswas detected by transcriptome sequencing.The differentially expressed genes were screened,and the functions and signaling pathways which differentially expressed genes were involved in were preliminarily analyzed through Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KECG)pathway enrichment analysis,and effect of DHHC7 on the invasive capacity of tumor cells was verified by Transwell invasion assay.Results There were 2099 differentially expressed genes between the knockout group and the control group,of which 1190 were downregulated and 909 were upregulated.Significantly enriched GO items included cell adhesion,cell membrane composition,etc.The results of KECC pathway enrichment analysis suggested that DHHC7 might be involved in extracelluar matrix-receptor interaction and cell adhesion molecular pathway.The result of transwell assay confirmed that ZDHHC7 knockout could inhibit the invasion of tumor cells.Conclusion DHHC7 may promote the invasiveness of colorectal cancer by regulating the destruction of extracellular matrix and the expression of cell adhesion molecules.展开更多
The intestinal lymphatic system is essential for lipid absorption, yet its regulatory mechanisms remain poorly understood. Here, we identify DHHC5, an Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferase,...The intestinal lymphatic system is essential for lipid absorption, yet its regulatory mechanisms remain poorly understood. Here, we identify DHHC5, an Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferase, as a critical regulator of intestinal lymphatic integrity and lipid uptake. Whole-body inducible Dhhc5 knockout (Dhhc5-IKO) mice were resistant to diet-induced obesity and exhibited impaired intestinal lipid absorption due to lymphatic dysfunction. Similar defects were observed upon specific knockout of DHHC5 in lymphatic endothelial cells (LECs), underscoring its cell-autonomous role. Mechanistically, DHHC5 facilitates vascular endothelial growth factor receptor 2 (VEGFR2) signaling by promoting its lipid raft localization in LECs. We further identified CRYBG1, an actin-binding protein, as the substrate of DHHC5. CRYBG1 interacts with VEGFR2, and its palmitoylation is required for the lipid raft localization of VEGFR2. These findings reveal a DHHC5–CRYBG1–VEGFR2 axis that governs intestinal lymphatic function and lipid absorption, providing new insights into the regulation of dietary lipid metabolism.展开更多
目的:探究棕榈酰转移酶DHHC7在结直肠癌侵袭过程中的作用及其机制。方法:敲除ZDHHC7基因的结肠癌细胞HCT116为敲除组,野生型HCT116细胞为对照组,采用转录组测序检测两组mRNA的表达情况。筛选差异表达基因,通过基因本体(Gene Ontology,GO...目的:探究棕榈酰转移酶DHHC7在结直肠癌侵袭过程中的作用及其机制。方法:敲除ZDHHC7基因的结肠癌细胞HCT116为敲除组,野生型HCT116细胞为对照组,采用转录组测序检测两组mRNA的表达情况。筛选差异表达基因,通过基因本体(Gene Ontology,GO)功能分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析对差异表达基因参与的功能和信号通路进行初步分析,通过Transwell侵袭实验验证DHHC7对肿瘤细胞侵袭能力的影响。结果:敲除组与对照组差异表达基因共有2099个,其中下调基因1190个,上调基因909个。显著富集的GO项目包括细胞黏附、细胞膜组成等。KEGG通路富集分析结果提示DHHC7可能参与细胞外基质受体相互作用和细胞黏附分子通路。Transwell实验结果证实敲除ZDHHC7可以抑制肿瘤细胞侵袭。结论:DHHC7可能通过调控细胞外基质的破坏和细胞黏附分子的表达,促进结直肠癌的侵袭。展开更多
Dwarf mutants are the crucial resources for molecular biology research and rice breeding. Here, a rice mutant, dwarf and deformed flower3（ddf3）, was identified in tissue culture of Oryza sativa cv. Dongjin. Compared...Dwarf mutants are the crucial resources for molecular biology research and rice breeding. Here, a rice mutant, dwarf and deformed flower3（ddf3）, was identified in tissue culture of Oryza sativa cv. Dongjin. Compared with wild type, the ddf3 mutant exhibited severe dwarfism, a greater number of tillers and significantly decreased fertility. In addition, leaf length, panicle length, and grain length, were significantly shorter. All internodes of ddf3 were shorter than those of wild type, and histological analysis revealed that internode cell elongation was significantly inhibited in ddf3. In the ddf3 mutant, pollen activity was significantly decreased, and the development of most stigmas was abnormal. Genetic analysis indicated that the ddf3 mutant phenotypes are controlled by a single or tightly linked nuclear genes. Using an F2 mapping population generated from a cross between ddf3 and Yangdao 6（9311）, the DDF3 gene was mapped to a 45.21-kb region between insertion-deletion（In Del） markers M15 and M16 on the long arm of chromosome 7. Sequencing revealed a 13.98-kbdeletion in this region in the ddf3 mutant genome that resulted in the complete or partial deletion of ZF（DHHC type zinc finger protein）, EP（expressed protein）, and FH2（actin-binding FH2 domain-containing protein） genes. Quantitative RT-PCR analyses revealed that in wild type, the transcript levels of FH2 were almost the same in all organs, while ZF was mainly expressed in the panicle, and no expression of EP was detected in any organ. Based on these results, ZF and FH2 could be potential DDF3 candidate genes involved in the regulation of rice morphology and flower organ development. Our work has laid the foundation for future functional analysis of these candidate genes and has provided a profitable gene resource for rice breeding for increased fertility in the future.展开更多
Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translatio...Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translational modifications is one of the key elements that allow the nervous system to adapt to environment stimulations. S-palmitoylation, an important lipid modification by post-translational addition of a long-chain fatty acid to a cysteine residue, regulates AMPA receptor trafficking, which dynamically affects multiple fundamental brain functions, such as learning and memory. In vivo, S-palmitoylation is controlled by palmitoyl acyl transferases and palmitoyl thioesterases.In this review, we highlight advances in the mechanisms for dynamic AMPA receptors palmitoylation,and discuss how palmitoylation affects AMPA receptors function at synapses in recent years.Pharmacological regulation of S-palmitoylation may serve as a novel therapeutic strategy for neurobiological diseases.展开更多
Protein palmitoylation is a widespread lipid modification in which one or more cysteine thiols on a substrate protein are modified to form a thioester with a palmitoyl group.This lipid modification is readily reversib...Protein palmitoylation is a widespread lipid modification in which one or more cysteine thiols on a substrate protein are modified to form a thioester with a palmitoyl group.This lipid modification is readily reversible;a feature of protein palmitoylation that allows for rapid regulation of the function of many cellular proteins.Mutations in palmitoyltransferases(PATs),the enzymes that catalyze the formation of this modification,are associated with a number of neurological diseases and cancer progression.This review summarizes the crucial role of palmitoylation in biological systems,the discovery of the DHHC protein family that catalyzes protein palmitoylation,and the development of methods for investigating the catalytic mechanism of PATs.展开更多
文摘Objective To explore the role and mechanism of palmitoyltransferase DHHC7 in colorectal cancer invasiveness.Methods Colorectacl ancer cell lines HCT116 with ZDHHC7 knocked out were the knockout group,and wild-type HCT116 cells were the control group.The mRNA expression of the two groupsswas detected by transcriptome sequencing.The differentially expressed genes were screened,and the functions and signaling pathways which differentially expressed genes were involved in were preliminarily analyzed through Gene Ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KECG)pathway enrichment analysis,and effect of DHHC7 on the invasive capacity of tumor cells was verified by Transwell invasion assay.Results There were 2099 differentially expressed genes between the knockout group and the control group,of which 1190 were downregulated and 909 were upregulated.Significantly enriched GO items included cell adhesion,cell membrane composition,etc.The results of KECC pathway enrichment analysis suggested that DHHC7 might be involved in extracelluar matrix-receptor interaction and cell adhesion molecular pathway.The result of transwell assay confirmed that ZDHHC7 knockout could inhibit the invasion of tumor cells.Conclusion DHHC7 may promote the invasiveness of colorectal cancer by regulating the destruction of extracellular matrix and the expression of cell adhesion molecules.
基金supported by the National Natural Science Foundation of China(32125022,32230053,92157301,and 32401059)the National Key R&D Program of China(2024YFA1306101 and 2020YFA0803601)the Shanghai Basic Research Field Project“Science and Technology Innovation Action Plan”(21JC1400400).
文摘The intestinal lymphatic system is essential for lipid absorption, yet its regulatory mechanisms remain poorly understood. Here, we identify DHHC5, an Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferase, as a critical regulator of intestinal lymphatic integrity and lipid uptake. Whole-body inducible Dhhc5 knockout (Dhhc5-IKO) mice were resistant to diet-induced obesity and exhibited impaired intestinal lipid absorption due to lymphatic dysfunction. Similar defects were observed upon specific knockout of DHHC5 in lymphatic endothelial cells (LECs), underscoring its cell-autonomous role. Mechanistically, DHHC5 facilitates vascular endothelial growth factor receptor 2 (VEGFR2) signaling by promoting its lipid raft localization in LECs. We further identified CRYBG1, an actin-binding protein, as the substrate of DHHC5. CRYBG1 interacts with VEGFR2, and its palmitoylation is required for the lipid raft localization of VEGFR2. These findings reveal a DHHC5–CRYBG1–VEGFR2 axis that governs intestinal lymphatic function and lipid absorption, providing new insights into the regulation of dietary lipid metabolism.
文摘目的:探究棕榈酰转移酶DHHC7在结直肠癌侵袭过程中的作用及其机制。方法:敲除ZDHHC7基因的结肠癌细胞HCT116为敲除组,野生型HCT116细胞为对照组,采用转录组测序检测两组mRNA的表达情况。筛选差异表达基因,通过基因本体(Gene Ontology,GO)功能分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析对差异表达基因参与的功能和信号通路进行初步分析,通过Transwell侵袭实验验证DHHC7对肿瘤细胞侵袭能力的影响。结果:敲除组与对照组差异表达基因共有2099个,其中下调基因1190个,上调基因909个。显著富集的GO项目包括细胞黏附、细胞膜组成等。KEGG通路富集分析结果提示DHHC7可能参与细胞外基质受体相互作用和细胞黏附分子通路。Transwell实验结果证实敲除ZDHHC7可以抑制肿瘤细胞侵袭。结论:DHHC7可能通过调控细胞外基质的破坏和细胞黏附分子的表达,促进结直肠癌的侵袭。
基金supported by the National Natural Science Foundation of China (31560350 and 31760350)the Science and Technology Program of Jiangxi, China (20171ACF60018)
文摘Dwarf mutants are the crucial resources for molecular biology research and rice breeding. Here, a rice mutant, dwarf and deformed flower3（ddf3）, was identified in tissue culture of Oryza sativa cv. Dongjin. Compared with wild type, the ddf3 mutant exhibited severe dwarfism, a greater number of tillers and significantly decreased fertility. In addition, leaf length, panicle length, and grain length, were significantly shorter. All internodes of ddf3 were shorter than those of wild type, and histological analysis revealed that internode cell elongation was significantly inhibited in ddf3. In the ddf3 mutant, pollen activity was significantly decreased, and the development of most stigmas was abnormal. Genetic analysis indicated that the ddf3 mutant phenotypes are controlled by a single or tightly linked nuclear genes. Using an F2 mapping population generated from a cross between ddf3 and Yangdao 6（9311）, the DDF3 gene was mapped to a 45.21-kb region between insertion-deletion（In Del） markers M15 and M16 on the long arm of chromosome 7. Sequencing revealed a 13.98-kbdeletion in this region in the ddf3 mutant genome that resulted in the complete or partial deletion of ZF（DHHC type zinc finger protein）, EP（expressed protein）, and FH2（actin-binding FH2 domain-containing protein） genes. Quantitative RT-PCR analyses revealed that in wild type, the transcript levels of FH2 were almost the same in all organs, while ZF was mainly expressed in the panicle, and no expression of EP was detected in any organ. Based on these results, ZF and FH2 could be potential DDF3 candidate genes involved in the regulation of rice morphology and flower organ development. Our work has laid the foundation for future functional analysis of these candidate genes and has provided a profitable gene resource for rice breeding for increased fertility in the future.
基金supported by grants from the National Basic Research Program of China (the 973 Program, No. 2013CB531303 to Dr. Jianguo Chen No. 2014CB744601 to Fang Wang)+3 种基金the National Natural Scientific Foundation of China (NSFC, No. 81222048 to Fang Wang No. 81302754 to Peng Fei Wu)supported by the International Science & Technology Cooperation Program of China (No. 2011DFA32670 to Jianguo Chen)PCSIRT (No. IRT13016)
文摘Glutamate acting on AMPA-type ionotropic glutamate receptor(AMPAR) mediates the majority of fast excitatory synaptic transmission in the mammalian central nervous system. Dynamic regulation of AMPAR by post-translational modifications is one of the key elements that allow the nervous system to adapt to environment stimulations. S-palmitoylation, an important lipid modification by post-translational addition of a long-chain fatty acid to a cysteine residue, regulates AMPA receptor trafficking, which dynamically affects multiple fundamental brain functions, such as learning and memory. In vivo, S-palmitoylation is controlled by palmitoyl acyl transferases and palmitoyl thioesterases.In this review, we highlight advances in the mechanisms for dynamic AMPA receptors palmitoylation,and discuss how palmitoylation affects AMPA receptors function at synapses in recent years.Pharmacological regulation of S-palmitoylation may serve as a novel therapeutic strategy for neurobiological diseases.
基金financially supported by the NIH R01 grant GM040602 (CAF)
文摘Protein palmitoylation is a widespread lipid modification in which one or more cysteine thiols on a substrate protein are modified to form a thioester with a palmitoyl group.This lipid modification is readily reversible;a feature of protein palmitoylation that allows for rapid regulation of the function of many cellular proteins.Mutations in palmitoyltransferases(PATs),the enzymes that catalyze the formation of this modification,are associated with a number of neurological diseases and cancer progression.This review summarizes the crucial role of palmitoylation in biological systems,the discovery of the DHHC protein family that catalyzes protein palmitoylation,and the development of methods for investigating the catalytic mechanism of PATs.
