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The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis 被引量:2
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作者 Xinxin Wang Yushu Hu Renshi Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第4期800-806,共7页
The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves t... The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory regions.However,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the disease.The disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized countries.The TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral sclerosis.This review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation). 展开更多
关键词 amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress PATHOGENESIS post-translational modification protein quality control system stress granules TAR dna-binding protein 43(TDP-43)
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Endonuclease-rolling circle amplification-based method for sensitive analysis of DNA-binding protein 被引量:4
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作者 Min Li Li Dong Rui Zhou +2 位作者 Hong Zhao Jin Ke Wang Zu Hong Lu 《Chinese Chemical Letters》 SCIE CAS CSCD 2009年第11期1315-1318,共4页
A sensitive approach for the qualitative detection of DNA-binding protein on the microarray was developed. DNA complexes in which a partial duplex region is formed from a biotin-primer and a circle single strand DNA ... A sensitive approach for the qualitative detection of DNA-binding protein on the microarray was developed. DNA complexes in which a partial duplex region is formed from a biotin-primer and a circle single strand DNA (ssDNA) were spotted on a microarray. The endonuclease recognition site (ERS) and the DNA-binding sites (DBS) were arranged side by side within the duplex region. The working principle of the detection system is described as follows: when the DNA-binding protein capture the DBS, the endonuclease could not attach to the ERS, and the immobilized primer in the DNA complex could be extended along the circle ssDNA by rolling circle amplification (RCA). When no protein protects the DBS, the ERS could be attacked by the endonuclease and subsequently no rolling circle amplification occurs. Thereby we can detect the sequence specific DNA-binding activity with high-sensitivity due to the signal amplification of RCA. 展开更多
关键词 Rolling circle amplification dna-binding protein MICROARRAY
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Role of the PEST sequence in the long-type GATA-6 DNA-binding protein expressed in human cancer cell lines
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作者 Kanako Obayashi Kayoko Takada +2 位作者 Kazuaki Ohashi Ayako Kobayashi-Ohashi Masatomo Maeda 《Advances in Bioscience and Biotechnology》 2012年第4期314-320,共7页
GATA-6 mRNA utilizes two Met-codons in frame as translational initiation codons in cultured mammalian cells. Deletion of the nucleotide sequence encoding the PEST sequence between the two initiation codons unusually r... GATA-6 mRNA utilizes two Met-codons in frame as translational initiation codons in cultured mammalian cells. Deletion of the nucleotide sequence encoding the PEST sequence between the two initiation codons unusually reduced the protein molecular size on SDS-polyacrylamide gel-electrophoresis. The reduced molecular size is ascribed to the molecular property of GATA-6, since both amino-and carboxy-lterminal tags introduced into GATA-6 were detected on the gel. This PEST sequence seems to contribute to expansion of the long-type GATA-6 molecule. The long-type GATA-6 containing the PEST sequence exhibits more activation potential than that without this sequence, the latter’s activity being similar to that of the short-type GATA-6. We further demonstrated that human colon and lung cancer cell lines express both the long-type GATA-6 and the short-type GATA-6 in their nuclei. 展开更多
关键词 dna-binding protein GATA-6 TRANSCRIPTION Factor Leaky RIBOSOME Scanning PEST Sequence Gel ELECTROPHORESIS
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Blood diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis
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作者 Yongting Lv Hongfu Li 《Neural Regeneration Research》 SCIE CAS 2025年第9期2556-2570,共15页
Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective d... Amyotrophic lateral sclerosis is a devastating neurodegenerative disease for which the current treatment approaches remain severely limited.The principal pathological alterations of the disease include the selective degeneration of motor neurons in the brain,brainstem,and spinal cord,as well as abnormal protein deposition in the cytoplasm of neurons and glial cells.The biological markers under extensive scrutiny are predominantly located in the cerebrospinal fluid,blood,and even urine.Among these biomarke rs,neurofilament proteins and glial fibrillary acidic protein most accurately reflect the pathologic changes in the central nervous system,while creatinine and creatine kinase mainly indicate pathological alterations in the peripheral nerves and muscles.Neurofilament light chain levels serve as an indicator of neuronal axonal injury that remain stable throughout disease progression and are a promising diagnostic and prognostic biomarker with high specificity and sensitivity.However,there are challenges in using neurofilament light chain to diffe rentiate amyotrophic lateral sclerosis from other central nervous system diseases with axonal injury.Glial fibrillary acidic protein predominantly reflects the degree of neuronal demyelination and is linked to non-motor symptoms of amyotrophic lateral sclerosis such as cognitive impairment,oxygen saturation,and the glomerular filtration rate.TAR DNA-binding protein 43,a pathological protein associated with amyotrophic lateral sclerosis,is emerging as a promising biomarker,particularly with advancements in exosome-related research.Evidence is currently lacking for the value of creatinine and creatine kinase as diagnostic markers;however,they show potential in predicting disease prognosis.Despite the vigorous progress made in the identification of amyotrophic lateral sclerosis biomarkers in recent years,the quest for definitive diagnostic and prognostic biomarke rs remains a formidable challenge.This review summarizes the latest research achievements concerning blood biomarkers in amyotrophic lateral sclerosis that can provide a more direct basis for the differential diagnosis and prognostic assessment of the disease beyond a reliance on clinical manifestations and electromyography findings. 展开更多
关键词 amyotrophic lateral sclerosis BIOMARKER blood biomarkers diagnosis glial fibrillary acidic protein neurofilament light chain PROGNOSIS TAR dna-binding protein 43
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Maintaining cholesterol homeostasis: Sterol regulatory element-binding proteins 被引量:17
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作者 LutzW.Weber MeinradBoll AndreasStampfl 《World Journal of Gastroenterology》 SCIE CAS CSCD 2004年第21期3081-3087,共7页
The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane pr... The molecular mechanism of how hepatocytes maintain cholesterol homeostasis has become much more transparent with the discovery of sterol regulatory element binding proteins (SREBPs) in recent years. These membrane proteins aremembers of the basic helix-loop-helix-leucine zipper (bHLHZip) family of transcription factors. They activate the expression of at least 30 genes involved in the synthesis of cholesterol and lipids. SREBPs are synthesized as precursor proteins in the endoplasmic reticulum (ER), where they form a complex with another protein, SREBP cleavage activating protein (SCAP). The SCAP molecule contains a sterol sensory domain. In the presence of high cellular sterol concentrations SCAP confines SREBP to the ER. With low cellular concentrations, SCAP escorts SREBP to activation in the Golgi. There, SREBP undergoes two proteolytic cleavage steps to release the mature, biologically active transcription factor, nuclear SREBP (nSREBP). nSREBP translocates to the nucleus and binds to sterol response elements (SRE) in the promoter/enhancer regions of target genes. Additional transcription factors are required to activate transcription of these genes. Three different SREBPs are known, SREBPs-1a, -1c and -2. SREBP-1a and -1c are isoforms produced from a single gene by alternate splicing. SREBP-2 is encoded by a different gene and does not display any isoforms. It appears that SREBPs alone, in the sequence described above, can exert complete control over cholesterol synthesis, whereas many additional factors (hormones, cytokines, etc.) are required for complete control of lipid metabolism. Medicinal manipulation of the SREBP/SCAP system is expected to prove highly beneficial in the management of cholesterol-related disease. 展开更多
关键词 ANIMALS CCAAT-Enhancer-Binding proteins CHOLESTEROL dna-binding proteins HOMEOSTASIS Humans Sterol Regulatory Element Binding protein 1 Sterol Regulatory Element Binding protein 2 Transcription Factors
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Protein synthesis modulation as a therapeutic approach for amyotrophic lateral sclerosis and frontotemporal dementia 被引量:1
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作者 Santiago E.Charif M.Florencia Vassallu +1 位作者 Lara Salvañal Lionel M.Igaz 《Neural Regeneration Research》 SCIE CAS CSCD 2022年第7期1423-1430,共8页
Protein synthesis is essential for cells to perform life metabolic processes.Pathological alterations of protein content can lead to particular diseases.Cells have an intrinsic array of mechanisms and pathways that ar... Protein synthesis is essential for cells to perform life metabolic processes.Pathological alterations of protein content can lead to particular diseases.Cells have an intrinsic array of mechanisms and pathways that are activated when protein misfolding,accumulation,aggregation or mislocalization occur.Some of them(like the unfolded protein response)represent complex interactions between endoplasmic reticulum sensors and elongation factors that tend to increase expression of chaperone proteins and/or repress translation in order to restore protein homeostasis(also known as proteostasis).This is even more important in neurons,as they are very susceptible to harmful effects associated with protein overload and proteostatic mechanisms are less effective with age.Several neurodegenerative pathologies such as Alzheimer’s,Parkinson’s,and Huntington’s diseases,amyotrophic lateral sclerosis and frontotemporal dementia exhibit a particular molecular signature of distinct,unbalanced protein overload.In amyotrophic lateral sclerosis and frontotemporal dementia,the majority of cases present intracellular inclusions of ubiquitinated transactive response DNA-binding protein of 43 kDa(TDP-43).TDP-43 is an RNA binding protein that participates in RNA metabolism,among other functions.Dysregulation of TDP-43(e.g.aggregation and mislocalization)can dramatically affect neurons,and this has been linked to disease development.Expression of amyotrophic lateral sclerosis/frontotemporal dementia TDP-43-related mutations in cellular and animal models has been shown to recapitulate key features of the amyotrophic lateral sclerosis/frontotemporal dementia disease spectrum.These variants can be causative of degeneration onset and progression.Most neurodegenerative diseases(including amyotrophic lateral sclerosis and frontotemporal dementia)have no cure at the moment;however,modulating translation has recently emerged as an attractive approach that can be performed at several steps(i.e.regulating activation of initiation and elongation factors,inhibiting unfolded protein response activation or inducing chaperone expression and activity).This review focuses on the features of protein imbalance in neurodegenerative disorders and the relevance of developing therapeutical compounds aiming at restoring proteostasis.We strive to highlight the importance of research on drugs that,not only restore protein imbalance without compromising translational activity of cells,but are also as safe as possible for the patients. 展开更多
关键词 amyotrophic lateral sclerosis frontotemporal dementia NEURODEGENERATION neurodegenerative diseases protein imbalance protein synthesis modulation PROTEOSTASIS therapeutical compounds transactive response dna-binding protein of 43 kDa TRANSLATION unfolded protein response
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Targeting prion-like protein spreading in neurodegenerative diseases
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作者 Zhaohui Zhang Shuke Nie Liam Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2018年第11期1875-1878,共4页
The infectious template-mediated protein conversion is a unique mechanism for the onset of rare and fatal neurodegenerative disorders known as transmissible spongiform encephalopathies, or prion diseases, which affect... The infectious template-mediated protein conversion is a unique mechanism for the onset of rare and fatal neurodegenerative disorders known as transmissible spongiform encephalopathies, or prion diseases, which affect humans and other animal species. However, emerging studies are now demonstrating prion-like mechanisms of self-propagation of protein misfolding in a number of common, non-infectious neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. It has been proposed that distinct and unrelated proteins(beta-amyloid, tau, α-synuclein, TAR DNA-binding protein 43 and huntingtin, etc.) associated with common neurodegenerative disorders can seed conversion and spread via cellto-cell transfer, sustaining the transmission of neurotoxic agents along a stereotypic route, sharing features at the heart of the intrinsic nature of prions. Here we review the most recent development on both the molecular mechanisms underlying the pathogenesis of prion-like neurodegenerative diseases as well as innovative methods and strategies for potential therapeutic applications. 展开更多
关键词 prion-like SYNUCLEIN tau TAR dna-binding protein 43 BETA-AMYLOID Parkinson's disease frontotemporal dementia amyotrophic lateral sclerosis Alzheimer's disease NEURODEGENERATION
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Dps Is a Stationary Phase-Specific Protein of <i>Escherichia coli</i>Nucleoid
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作者 Ali Azam Talukder Akira Ishihama 《Advances in Microbiology》 2014年第15期1095-1104,共10页
Bacterial genomic DNA is highly organized into one or few compacted bodies known as nucleoid, which is composed of DNA, RNA and several DNA-binding proteins. These DNA-binding proteins require essential alterations in... Bacterial genomic DNA is highly organized into one or few compacted bodies known as nucleoid, which is composed of DNA, RNA and several DNA-binding proteins. These DNA-binding proteins require essential alterations in their expression during stationary phase of growth in order to re-spond to stressful environmental conditions. Dps (DNA-binding protein from starved cells) is one of such DNA-binding proteins, which accumulates most when E. coli cells reach to the stationary phase. Here, we have characterized Dps protein under various growth phases. Immunofluorescent microscopic observation reveals that Dps plays a key role in final round of genome compaction during the stationary phase. Similar results are also obtained by Western immunoblot analysis, after quantification of Dps protein from the exponential phase and early stationary phase nucleoid bound fractions, separated by sucrose density gradient centrifugation. Our results support the conclusion that Dps occupies more than half of the stationary phase nucleoid in E. coli. 展开更多
关键词 DPS dna-binding protein Stationary Phase E. COLI NUCLEOID
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Isolation and identification of proteins binding to the major breakpoint region(mbr) of bcl2 gene
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作者 Nan Yang Yujie Sun Changyan Ma 《Journal of Nanjing Medical University》 2009年第4期236-240,共5页
Objective: We have previously found that mbr is a regulatory element of the bcl2 gene. The objective of this study is to isolate and identify the proteins binding to the 37 mbr in the 3 ' -end of the mbr. Methods: ... Objective: We have previously found that mbr is a regulatory element of the bcl2 gene. The objective of this study is to isolate and identify the proteins binding to the 37 mbr in the 3 ' -end of the mbr. Methods: Streptavidin magnetic particles were ligated to concatameric oligonucleotides of 37 mbr and incubated with the nuclear extracts of Jurkat cells. The DNA-binding proteins were eluted and then resolved by SDS-PAGE. After silver staining, the protein bands were excised and subjected to MALDI-TOF MS. Results: Several protein bands were detected after the isolation with magnetic particles, and Splicing factor, proline- and glutamine-rich(SFPQ), Poly(ADP-ribose) polymerase I(PARP), and promyelocytic leukemia protein(PML) were identified by MALDI-TOF MS. Conclusion: Several proteins were isolated and identified from the 37 mbr-protein complex. Results of this study establish a foundation for further study of the mechanisms by which mbr executes its regulatory function. 展开更多
关键词 bcl2 gene 37 mbr dna-binding protein
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Cloning, expression, purification and characterization of replication protein from plasmid pGP2 from Acetobacter estunensis
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作者 Peter Grones Jozef Grones 《Advances in Bioscience and Biotechnology》 2010年第5期417-425,共9页
The Acetobacter estunensis Rep34 protein participates in the replication of bacterial plasmid pGP2. The Rep34 protein of the A. estunensis, was cloned to the expression vector, that ensure fusion with a His-tag sequen... The Acetobacter estunensis Rep34 protein participates in the replication of bacterial plasmid pGP2. The Rep34 protein of the A. estunensis, was cloned to the expression vector, that ensure fusion with a His-tag sequence (Rep34 His-tagged), over-expressed in Escherichia coli and purified by metal-affinity chromatography to yield a highly purified and active protein. On this purified protein number different activities and motifs were detected. DNA band-shift assays showed that the Rep34 His-tagged protein bound to the regulation region for replication on the linear double-stranded DNA. In the protein was determined phosphatase activity, ATPase activity and protein is possible to unwind double strand DNA. 展开更多
关键词 ACETOBACTER Estunensis Rep34 protein dna-binding ACTIVITY ATPase ACTIVITY PHOSPHATASE ACTIVITY UNWINDING ACTIVITY
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5-Hydroxytryptamine:a potential therapeutic target in amyotrophic lateral sclerosis 被引量:2
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作者 Shi-Shi Jiang Meng-Ni Gong +5 位作者 Wei Rao Wen Chai Wen-Zhi Chen Xiong Zhang Hong-Bing Nie Ren-Shi Xu 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第9期2047-2055,共9页
Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis(ALS) is closely linked to 5-hydroxytryptamine(5-HT).To investigate this further,we administered 5-HT receptor antagonists to SOD1*... Previous studies have indicated that the pathogenesis of amyotrophic lateral sclerosis(ALS) is closely linked to 5-hydroxytryptamine(5-HT).To investigate this further,we administered 5-HT receptor antagonists to SOD1*G93A transgenic(ALS mouse model) and wide-type mice.This involved intraperitoneal injections of either granisetron,piboserod,or ritanserin,which inhibit the 5-HT3,5-HT4,and 5-HT2 receptors,respectively.The transgenic mice were found to have fewer5-HT-positive cells in the spinal cord compared with wide-type mice.We found that the administration of granisetron reduced the body weight of the transgenic mice,while piboserod and ritanserin worsened the motor functioning,as assessed using a hanging wire test.However,none of the 5-HT receptor antagonists affected the disease progression.We analyzed the distribution and/or expression of TAR DNA binding protein 43(TDP-43) and superoxide dismutase 1 G93A(SOD1-G93A),which fo rm abnormal aggregates in ALS.We found that the expression of these proteins increased following the administration of all three 5-HT receptor antagonists.In addition,the disease-related mislocalization of TD P-43 to the cytoplasm increased markedly for all three drugs.In ce rtain anatomical regions,the 5-HT receptor antagonists also led to a marked increase in the number of astrocytes and microglia and a decrease in the number of neurons.These results indicate that 5-HT deficiency may play a role in the pathogenesis of amyotrophic lateral sclerosis by inducing the abnormal expression and/or distribution of TDP-43 and SOD1-G93A and by activating glial cells.5-HT co uld therefore be a potential therapeutic target for amyotrophic lateral sclerosis. 展开更多
关键词 5-HYDROXYTRYPTAMINE amyotrophic lateral sclerosis ASTROCYTES GRANISETRON MICROGLIA neuron piboserod RITANSERIN SOD1-G93A TAR dna-binding protein 43
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TAR DNA-Binding Protein 43 is Cleaved by the Protease 3C of Enterovirus A71 被引量:1
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作者 Xiaoman Wo Yuan Yuan +8 位作者 Yong Xu Yang Chen Yao Wang Shuoxuan Zhao Lexun Lin Xiaoyan Zhong Yan Wang Zhaohua Zhong Wenran Zhao 《Virologica Sinica》 SCIE CAS CSCD 2021年第1期95-103,共9页
Enterovirus A71(EV-A71)is one of the etiological pathogens leading to hand,foot,and mouth disease(HFMD),which can cause severe neurological complications.The neuropathogenesis of EV-A71 infection is not well understoo... Enterovirus A71(EV-A71)is one of the etiological pathogens leading to hand,foot,and mouth disease(HFMD),which can cause severe neurological complications.The neuropathogenesis of EV-A71 infection is not well understood.The mislocalization and aggregation of TAR DNA-binding protein 43(TDP-43)is the pathological hallmark of amyotrophic lateral sclerosis(ALS).However,whether TDP-43 was impacted by EV-A71 infection is unknown.This study demonstrated that TDP-43 was cleaved during EV-A71 infection.The cleavage of TDP-43 requires EV-A71 replication rather than the activated caspases due to viral infection.TDP-43 is cleaved by viral protease 3 C between the residues 331 Q and332 S,while mutated TDP-43(Q331 A)was not cleaved.In addition,mutated 3 C which lacks the protease activity failed to induce TDP-43 cleavage.We also found that TDP-43 was translocated from the nucleus to the cytoplasm,and the mislocalization of TDP-43 was induced by viral protease 2 A rather than 3 C.Taken together,we demonstrated that TDP-43 was cleaved by viral protease and translocated to the cytoplasm during EV-A71 infection,implicating the possible involvement of TDP-43 in the pathogenesis of EV-A71 infection. 展开更多
关键词 Enterovirus A71(EV-A71) TAR dna-binding protein 43(TDP-43) 3C protease 2A protease
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A DNA-Binding Bromodomain-Containing Protein Interacts with and Reduces Rx1-Mediated Immune Response to Potato Virus X
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作者 Octavina C.A.Sukarta Philip D.Townsend +6 位作者 Alexander Llewelyn Christopher H.Dixon Erik J.Slootweg Lars-Olof Pålsson Frank L.W.Takken Aska Goverse Martin J.Cann 《Plant Communications》 2020年第4期101-114,共14页
Plant NLR proteins enable the immune systemto recognize and respond to pathogen attack.An early consequence of immune activation is transcriptional reprogramming.SomeNLRs have been shownto act in the nucleus and inter... Plant NLR proteins enable the immune systemto recognize and respond to pathogen attack.An early consequence of immune activation is transcriptional reprogramming.SomeNLRs have been shownto act in the nucleus and interact with transcription factors.The Rx1 NLR protein of potato binds and distorts doublestranded DNA.However,the components of the chromatin-localized Rx1 complex are largely unknown.Here,we report a physical and functional interaction between Rx1 and NbDBCP,a bromodomaincontaining chromatin-interacting protein.NbDBCP accumulates in the nucleoplasmand nucleolus,interacts with chromatin,and redistributes Rx1 tothe nucleolus in a subpopulation of imaged cells.Rx1 overexpression reduces the interaction between NbDBCP and chromatin.NbDBCP is a negative regulator of Rx1-mediated immune responses to potato virus X(PVX),and this activity requires an intact bromodomain.Previously,Rx1 has been shown to regulate the DNA-binding activity of a Golden2-like transcription factor,NbGlk1.Rx1 and NbDBCP act synergistically to reduce NbGlk1 DNA binding,suggesting a mode of action for NbDBCP’s inhibitory effect on immunity.This study provides new mechanistic insight into the mechanism by which a chromatin-localized NLR complex co-ordinates immune signaling after pathogen perception. 展开更多
关键词 cellular immune response dna-binding protein host-pathogen interaction plant biochemistry plant defense plant virus
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Changes of NF-kB,p53,Bcl-2 and caspase in apoptosis induced by JTE-522 in human gastric adenocarcinoma cell line AGS cells:role of reactive oxygen species 被引量:58
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作者 Hong-Liang Li Xiao-Hong Li Yan-Qing L Chun-Ling Ye Xian-Da Ren,Department of Pharmacology,Jinan University Pharmacy College,Guangzhou 510632,Guangdong,China Dan-Dan Chen,Department of Cardiology,First Affiliated Hospital,Zhongshan University,Guangzhou 510089,Guangdong,China Hai-Wei Zhang,Department of Pathology,Jinan University Medical College,Guangzhou 510632,Guangdong,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2002年第3期431-435,共5页
AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture,... AIM: To identify whether JTE-522 can induce apoptosis in AGS cells and ROS also involved in the process, and to investigate the changes in NF-kB, p53, bcl-2 and caspase in the apoptosis process. METHODS: Cell culture, MTT, Electromicroscopy, agarose gel electrophoresis, lucigenin, Western blot and electrophoretic mobility shift assay (EMSA) analysis were employed to investigate the effect of JTE-522 on cell proliferation and apoptosis in AGS cells and related molecular mechanisms. RESULTS: JTE-522 inhibited the growth of AGS cells and induced the apoptosis. Lucigenin assay showed the generation of ROS in cells under incubation with JTE-522. The increased ROS generation might contribute to the induction of AGS cells to apoptosis. EMSA and Western blot revealed that NF-kB activity was almost completely inhibited by preventing the degradation of IkBalpha. Additionally, by using Western blot we confirmed that the level of bcl-2 was decreased, whereas p53 showed a great increase following JTE-522 treatment. Their changes were in a dose-dependent manner. CONCLUSION: These findings suggest that reactive oxygen species, NF-kB, p53, bcl-2 and caspase-3 may play an important role in the induction of apoptosis in AGS cells after treatment with JTE-522. 展开更多
关键词 I-kappa B proteins Adenocarcinoma APOPTOSIS BENZENESULFONATES CASPASES Cell Division dna-binding proteins Humans NF-kappa B OXAZOLES Proto-Oncogene proteins c-bcl-2 Reactive Oxygen Species Research Support Non-U.S. Gov't Stomach Neoplasms Tumor Cells Cultured Tumor Suppressor protein p53
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Effects of histone acetylation and DNA methylation on p21^(WAF1)regulation 被引量:25
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作者 FangJY LuYY 《World Journal of Gastroenterology》 SCIE CAS CSCD 2002年第3期400-405,共6页
Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play ... Cell cycle progression is regulated by interactions between cyclins and cyclin-dependent kinases (CDKs). p21(WAF1) is one of the CIP/KIP family which inhibits CDKs activity. Increased expression of p21(WAF1) may play an important role in the growth arrest induced in transformed cells. Although the stability of the p21( WAF1) mRNA could be altered by different signals, cell differentiation and numerous influencing factors. However, recent studies suggest that two known mechanisms of epigenesis, i.e.gene inactivation by methylation in promoter region and changes to an inactive chromatin by histone deacetylation, seem to be the best candidate mechanisms for inactivation of p21( WAF1). To date, almost no coding region p21(WAF1) mutations have been found in tumor cells, despite extensive screening of hundreds of various tumors. Hypermethylation of the p21(WAF1) promoter region may represent an alternative mechanism by which the p21(WAF1/CIP1) gene can be inactivated. The reduction of cellular DNMT protein levels also induces a corresponding rapid increase in the cell cycle regulator p21(WAF1) protein demonstrating a regulatory link between DNMT and p21(WAF1) which is independent of methylation of DNA. Both histone hyperacetylation and hypoacetylation appear to be important in the carcinoma process, and induction of the p21(WAF1) gene by histone hyperacetylation may be a mechanism by which dietary fiber prevents carcinogenesis. Here, we review the influence of histone acetylation and DNA methylation on p21(WAF1) transcription, and affection of pathways or factors associated such as p 53, E2A, Sp1 as well as several histone deacetylation inhibitors. 展开更多
关键词 DNA Methylation dna-binding proteins Acetylation ACETYLTRANSFERASES Base Sequence Basic Helix-Loop-Helix Transcription Factors Cell Cycle proteins Cell Transformation Neoplastic CpG Islands Cyclin-Dependent Kinase Inhibitor p21 CYCLINS DNA Histone Acetyltransferases HISTONES Humans Molecular Sequence Data Nuclear proteins Signal Transduction Sp1 Transcription Factor TRANS-ACTIVATORS Transcription Factors
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Transcription factor EGR-1 inhibits growth of hepatocellular carcinoma and esophageal carcinoma cell lines 被引量:24
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作者 Miao-Wang Hao Li Liu,Department of Internal Medicine,Tangdu Hospital,Xi’an 710038,Shaanxi Province,China Ying-Rui Liang Ming-Yao Wu Huan-Xing Yang,Department of Pathology,Medical College of Shantou University,Shantou 515031,Guangdong Province,China Yan-Fang Liu,Department of Pathology,Fourth Military Medical University,Xi’an 710032,Shaanxi Province,China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2002年第2期203-207,共5页
AIM: The transcription factor EGR-1 (early growth response gene-1) plays an important role in cell growth, differentiation and development. It has identified that EGR-1 has significant transformation suppression activ... AIM: The transcription factor EGR-1 (early growth response gene-1) plays an important role in cell growth, differentiation and development. It has identified that EGR-1 has significant transformation suppression activity in some neoplasms, such as fibrosarcoma, breast carcinoma. This experiment was designed to investigate the role of egr-1 in the cancerous process of hepatocellular carcinoma (HCC) and esophageal carcinoma (EC), and then to appraise the effects of EGR-1 on the growth of these tumor cells. METHODS: Firstly, the transcription and expression of egr-1 in HCC and EC, paracancerous tissues and their normal counterpart parts were detected by in situ hybridization and immunohistochemistry, with normal human breast and mouse brain tissues as positive controls. Egr-1 gene was then transfected into HCC (HHCC, SMMC7721) and EC (ECa109) cell lines in which no egr-1 transcription and expression were present. The cell growth speed, FCM cell cycle, plate clone formation and tumorigenicity in nude mice were observed and the controls were the cell lines transfected with vector only. RESULTS: Little or no egr-1 transcription and expression were detected in HCC, EC and normal liver tissues. The expression of egr-1 were found higher in hepatocellular paracancerous tissue (transcription level P=0.000; expression level P=0.143, probably because fewer in number of cases) and dysplastic tissue of esophageal cancer (transcription level P=0.000; expression level P=0.001). The growth rate of egr-1-transfected HHCC (HCC cell line) cells and ECa109 (EC cell line) cells was much slower than that of the controls. The proportion of S phase cell, clone formation and tumorigenicity were significantly lower than these of the controls' (decreased 45.5% in HHCC cells and 34.1% in ECa109 cells; 46.6% and 41.8%; 80.4% and 72.6% respectively). There were no obvious differences between SMMC7721 (HCC) egr-1-transfected cells and the controls with regard to the above items. CONCLUSION: The decreased expression of egr-1 might play a role in the dysregulation of normal growth in the cancerous process of HCC and EC. Egr-1 gene of transfected HHCC and ECa109 cells showed obvious suppression of the cell growth and malignant phenotypes, but no suppression in SMMC7721 (HCC cell line) cells. 展开更多
关键词 Animals Carcinoma Hepatocellular Cell Division Cell Transplantation dna-binding proteins Early Growth Response protein 1 Esophageal Neoplasms Humans Immediate-Early proteins In Situ Hybridization Liver Neoplasms MICE Mice Nude Neoplasm Transplantation Research Support Non-U.S. Gov't Transcription Factors Tumor Cells Cultured
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Experimental and clinic-opathologic study on the relationship between transcription factor Egr-1 and esophageal carcinoma 被引量:20
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作者 Ming-Yao Wu Mao-Huai Chen Ying-Rui Liang Guo-Zhao Meng Huan-Xing Yang Chu-Xiang Zhuang Department of Pathology,Shantou University Medical College,Shantou 515031,Guangdong Province,China Supported by the National Natural Science Foundation of China,No.39670298. 《World Journal of Gastroenterology》 SCIE CAS CSCD 2001年第4期490-495,共6页
AIM: To observe the growth suppression effect of exogenous introduction of early growth response gene-1 (Egr-1 gene) on esophageal carcinoma tissue as well as on esophageal carcinoma cell line Eca109 and to explore th... AIM: To observe the growth suppression effect of exogenous introduction of early growth response gene-1 (Egr-1 gene) on esophageal carcinoma tissue as well as on esophageal carcinoma cell line Eca109 and to explore the potential application of Egr-1 gene in gene therapy of tumor. METHODS: Eukaryotic expression vector of PCMV-Egr-1 plasmid was introduced into Eca109 cell line which expressed no Egr-1 protein originally with lipofectamine transfection method. The introduction and expression of PCMV-Egr-1 plasmid into Eca109 cell line was confirmed by G418 selection culture, PCR amplification of neogene contained in the vector, Western blot analysis and immunocytochemical analysis. The cell growth curve, soft agar colony formation rate and tumorigenicity in SCID mice were examined to demonstrate the growth suppression effect of exogenous Egr-1 gene on Eca109 cell line. The Egr-1 mRNA and Egr-1 protein were also detected in 50 surgical specimens of esophageal carcinoma by in situ hybridization and immunohistochemistry. RESULTS: Exogenous Egr-1 gene was introduced successfully into Eca109 cell line and expressed Egr-1 protein stably. The transfected Eca109 cell line grew more slowly than control Eca109 as shown by cell growth curves, the soft agar colony formation rate (4.0% vs 6.9%, P 【 0.01) and the average growth rate of tumor in SCID mice (35.5 +/- 7.6 vs 65.8 +/- 7.6, P 【 0.05). The expression level of Egr-1 mRNA and protein significantly increased in dysplastic epithelia adjacent to cancer rather than in cancer tissues (65.8% vs 20.0% by ISH and 57.9% vs 0.01). CONCLUSION: Exogenous Egr-1 gene shows the strong effect of growth inhibition in Eca109 cell line. Egr-1 in the cancer tissue shows down-regulated expression that supports the inhibited function of Egr-1 in cancer growth and suggests Egr-1 may have an important role in gene therapy of esophageal carcinoma. 展开更多
关键词 Gene Expression Regulation Neoplastic Animals Blotting Western Carcinogenicity Tests Cell Division dna-binding proteins Early Growth Response protein 1 Esophageal Neoplasms Humans Immediate-Early proteins MICE Mice SCID Plasmids Research Support Non-U.S. Gov't Transcription Factors Transfection Tumor Cells Cultured
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Transcription factor changes following long term cerebral ischemia/reperfusion injury 被引量:2
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作者 Hongbo Zhang Weijuan Gao +2 位作者 Tao Qian Jinglong Tang Jun Li 《Neural Regeneration Research》 SCIE CAS CSCD 2013年第10期916-921,共6页
The present study established a rat model of cerebral ischemia/reperfusion injury using four-vessel occlusion and found that hippocampal CA1 neuronal morphology was damaged, and that there were reductions in hippocamp... The present study established a rat model of cerebral ischemia/reperfusion injury using four-vessel occlusion and found that hippocampal CA1 neuronal morphology was damaged, and that there were reductions in hippocampal neuron number and DNA-binding activity of cAMP response element binding protein and CCAAT/enhancer binding protein, accompanied by decreased learning and memory ability. These findings indicate that decline of hippocampal cAMP response element binding protein and CCAAT/enhancer binding protein DNA-binding activities may contribute to neuronal injury and learning and memory ability reduction induced by cerebral ischemia/reperfusion injury. 展开更多
关键词 neural regeneration brain injury cerebral ischemia/reperfusion hippocampus cAMP responseelement binding protein CCAAT/enhancer binding protein dna-binding activity brain grants-supported paper NEUROREGENERATION
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Induction of apoptosis by TPA and VP-16 is through translocation of TR3 被引量:14
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作者 LiuS WuQ 《World Journal of Gastroenterology》 SCIE CAS CSCD 2002年第3期446-450,共5页
AIM: To investigate the role of TR3 in induction of apoptosis in gastric cancer cells. METHODS: Human gastric cancer cell line, MGC80-3, was used. Expression of TR3 mRNA and its protein was detected by Northern blot a... AIM: To investigate the role of TR3 in induction of apoptosis in gastric cancer cells. METHODS: Human gastric cancer cell line, MGC80-3, was used. Expression of TR3 mRNA and its protein was detected by Northern blot and Western blot. Localization of TR3 protein was showed by immunofluorescence analysis under laser-scanning confocal microscope. Apoptotic morphology was observed by DAPI fluorescence staining, and apoptotic index was counted among 1000 cells randomly. Stable transfection assay was carried out by Lipofectamine. RESULTS: Treatment of MGC80-3 cells with TPA and VP-16 resulted in apoptosis, accompanied by the repression of Bcl-2 protein in a time-dependent manner. At the same time, TPA and VP-16 also up-regulated expression level of TR3 mRNA in MGC80-3 cells that expressed TR3 mRNA. When antisense-TR3 expression vector was transfected into the cells, expression of TR3 protein was repressed. In this case, TPA and VP-16 did not induce apoptosis. In addition, TPA and VP-16-induced apoptosis involved in translocation of TR3. In MGC80-3 cells, TR3 localized concentrative in nucleus, after treatment of cells with TPA and VP-16, TR3 translocated from nucleus to cytosol obviously. However, when this nuclear translocation was blocked by LMB, apoptosis was not occurred in MGC80-3 cells even in the presence of TPA and VP-16. CONCLUSION: Induction of apoptosis by TPA and VP-16 is through induction of TR3 expression and translocation of TR3 from nucleus to cytosol, which may be a novel signal pathway for TR3, and represent the new biological function of TR3 to exert its effect on apoptosis in gastric cancer cells. 展开更多
关键词 Active Transport Cell Nucleus APOPTOSIS dna-binding proteins ETOPOSIDE Gene Expression RNA Messenger RNA Neoplasm Receptors Cytoplasmic and Nuclear Receptors Steroid Research Support Non-U.S. Gov't Signal Transduction Stomach Neoplasms Tetradecanoylphorbol Acetate Transcription Factors Tumor Cells Cultured
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Genome-Wide Identification and Characterization of the <i>Dof</i>Transcription Factor Gene Family in <i>Phaseolus vulgaris</i>L. 被引量:1
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作者 Tania Mayumi Ito Claudia Borsari Trevizan +1 位作者 Tiago Benedito dos Santos Silvia Graciele Hülse de Souza 《American Journal of Plant Sciences》 2017年第12期3233-3257,共25页
The Dof (DNA-binding with one finger) proteins are a class of plant-specific transcription factors that can trigger several processes involved in plant growth and development, as well as in stress responses. Here, we ... The Dof (DNA-binding with one finger) proteins are a class of plant-specific transcription factors that can trigger several processes involved in plant growth and development, as well as in stress responses. Here, we performed a systematic bioinformatics analysis to characterize all Dof genes in common bean, which included analysis of the genome sequence, conserved protein domains, chromosomal locations, subcellular locations, phylogenetic relationships, gene duplications, and gene expression profiles in different tissues. Bioinformatics analysis revealed 36 putative genes related to PvDof that were classified into seven subfamilies (A, B1, B2, C1, C2, D1, and, D2) by comparative phylogenetic analysis. Based on our genome duplication analysis, a total of 36 genes were found to be distributed on all 11 chromosomes, and they expanded through gene duplication in tandem, suggesting the involvement of segmental duplication events in the evolutionary process. Synteny events and phylogenetic comparisons of the Dof proteins of common bean with those of A. thaliana, O. sativa, and G. max L. led to the identification of several orthologous and paralogous genes, which provided further insight into the diversity of the evolutionary characteristics of genes of this family in other plant species. Expression profiles revealed that most of the PvDof genes were expressed in different tissues, indicating that PvDof genes may be involved in various physiological functions during plant development. The results of this study provide additional information and potential biotechnological resources for further understanding the molecular basis of this gene family and consequently improvement of common bean crops. 展开更多
关键词 Common BEAN dna-binding with One Finger (Dof) Domain proteins Tran-scription Factor
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