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莪术油注射液对人卵巢癌skov3细胞胀亡及bcl-2表达的影响  [PDF]
杨美春,方刚,李林,覃振林,钟振国,杨思源,汤红丽
中国中医药信息杂志 , 2009,
Abstract: 目的观察莪术油注射液对人卵巢癌skov3细胞胀亡指数及bcl-2表达的影响,探讨莪术油注射液致人卵巢癌skov3细胞胀亡的机制。方法以不同浓度莪术油注射液作用人卵巢癌skov3细胞后,通过荧光显微镜观察细胞核变化、透射电镜计算细胞胀亡指数、琼脂糖凝胶电泳观察细胞dna断裂情况、免疫组化观察细胞bcl-2基因的表达。结果人卵巢癌skov3细胞经莪术油注射液作用48h后,荧光显微镜观察到胀亡细胞出现细胞肿胀,体积增大,胞膜面积缩小,核染色质分散扩大;细胞胀亡指数随浓度的增加而增大,呈量效关系;电泳观察dna呈弥漫型;bcl-2基因表达下调。结论莪术油注射液可使人卵巢癌skov3细胞随浓度的增加而胀亡指数增大,并可下调bcl-2基因表达,提示下调bcl-2基因表达可能是莪术油注射液致skov3细胞胀亡的作用机制之一。
论宋亡“诗史”  [PDF]
方勇
浙江大学学报(人文社会科学版) , 2001,
Abstract: ?宋末士子在经历了空前的鼎革动乱之后,对杜甫“诗史”精神有了比唐人更为深刻的认识。而在艺术形式方面,他们对杜甫“诗史”又有了重大的突破和发展。尤其是汪元量主要用联章组诗手法创作出来的宋亡“诗史”长卷,舒岳祥主要用以序代题手法创作出来的反映宋末元初东南沿海地区动乱现实的“诗史”巨卷,则更成了我国“诗史”发展史上的两座里程碑。
《史记》亡缺研究述评  [PDF]
李景文,宋立
图书情报工作 , 2009,
Abstract: ?针对两千年来历代学者对《史记》亡佚情况进行考辨的情况,分类梳理历代学者的研究结果,将其归纳为“十篇全亡说”、“部分亡佚说”、“十篇未亡说”三大类进行述评,并提出今后研究应当关注的方向。
The Role of egr1 in Early Zebrafish Retinogenesis  [PDF]
Liyun Zhang, Jin Cho, Devon Ptak, Yuk Fai Leung
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0056108
Abstract: Proper retinal cell differentiation is essential for establishing a functional retina. The purpose of this study is to investigate the role of early growth response 1 (egr1), a transcription factor (TF) that has been reported to control eye development and function, on retinal differentiation in zebrafish. Specifically, cellular changes in the Egr1-knockdown retinas were characterized by immunohistochemistry at 72 and 120 hours post-fertilization (hpf). The results indicate that Egr1 knockdown specifically suppressed the differentiation of subtypes of amacrine cells (ACs) and horizontal cells (HCs), including Parvalbumin- and GABA-positive ACs as well as Islet1-positive HCs. In addition, the knockdown induced a general delay of development of the other retinal cell types. These differentiation problems, particularly the ones with the ACs and HCs, also compromised the integrity of the inner and outer plexiform layers. In the Egr1-knockdown retinas, the expression of ptf1a, a TF that controls the specification of ACs and HCs, was prolonged and found in ectopic locations in the retina up to 72 hpf. Then, it became restricted to the proliferative marginal zone as in the control retinas at 120 hpf. This abnormal and prolonged expression of ptf1a during retinogenesis might affect the differentiation of ACs and HCs in the Egr1-knockdown retinas.
MAML1 Acts Cooperatively with EGR1 to Activate EGR1-Regulated Promoters: Implications for Nephrogenesis and the Development of Renal Cancer  [PDF]
Magnus L. Hansson, Stefanie Behmer, Rebecca Ceder, Sadollah Mohammadi, Giulio Preta, Roland C. Grafstr?m, Bengt Fadeel, Annika E. Wallberg
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0046001
Abstract: Mastermind-like 1 (MAML1) is a transcriptional coregulator of activators in various signaling pathways, such as Notch, p53, myocyte enhancer factor 2C (MEF2C) and beta-catenin. In earlier studies, we demonstrated that MAML1 enhanced p300 acetyltransferase activity, which increased the acetylation of Notch by p300. In this study, we show that MAML1 strongly induced acetylation of the transcription factor early growth response-1 (EGR1) by p300, and increased EGR1 protein expression in embryonic kidney cells. EGR1 mRNA transcripts were also upregulated in the presence of MAML1. We show that MAML1 physically interacted with, and acted cooperatively with EGR1 to increase transcriptional activity of the EGR1 and p300 promoters, which both contain EGR1 binding sites. Bioinformatics assessment revealed a correlation between p300, EGR1 and MAML1 copy number and mRNA alterations in renal clear cell carcinoma and p300, EGR1 and MAML1 gene alterations were associated with increased overall survival. Our findings suggest MAML1 may be a component of the transcriptional networks which regulate EGR1 target genes during nephrogenesis and could also have implications for the development of renal cell carcinoma.
EGR1 is essential for transcriptional regulation of BMPR2  [PDF]
Radhika Gaddipati, James D. West, James E. Loyd, Thomas Blackwell, Kirsten A. Lane, Nicole M. Lane, Kirk B. Lane
American Journal of Molecular Biology (AJMB) , 2011, DOI: 10.4236/ajmb.2011.13014
Abstract: In this study, RLM-RACE was used to identify the transcriptional start site 387 bp upstream of the translational start. Evolutionarily conserved transcription factor binding sites were identified, and a series of luciferase reporter constructs driven by BMPR2 promoter elements used to determine their functional relevance. We found the promoter area from 983 bp to 90 bp upstream of the transcriptional start gave maximal activity, greater than longer constructs, with an area between 570 bp and 290 bp upstream of the transcriptional start containing an important repressor element. To characterize this repressor, we used a combination of EMSA, mutation of the EGR1 binding site, transfection with EGR1 and NAB1 constructs, and mutation of the NAB1 binding site within the EGR1 protein. From this we conclude that EGR1 is essential to BMPR2 transcription, but that NAB1 binding to EGR1 causes it to act as a repressor.
The Transcription Factor EGR1 Localizes to the Nucleolus and Is Linked to Suppression of Ribosomal Precursor Synthesis  [PDF]
Donatella Ponti, Gian Carlo Bellenchi, Rosa Puca, Daniela Bastianelli, Marella Maroder, Giuseppe Ragona, Pascal Roussel, Marc Thiry, Dan Mercola, Antonella Calogero
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096037
Abstract: EGR1 is an immediate early gene with a wide range of activities as transcription factor, spanning from regulation of cell growth to differentiation. Numerous studies show that EGR1 either promotes the proliferation of stimulated cells or suppresses the tumorigenic growth of transformed cells. Upon interaction with ARF, EGR1 is sumoylated and acquires the ability to bind to specific targets such as PTEN and in turn to regulate cell growth. ARF is mainly localized to the periphery of nucleolus where is able to negatively regulate ribosome biogenesis. Since EGR1 colocalizes with ARF under IGF-1 stimulation we asked the question of whether EGR1 also relocate to the nucleolus to interact with ARF. Here we show that EGR1 colocalizes with nucleolar markers such as fibrillarin and B23 in the presence of ARF. Western analysis of nucleolar extracts from HeLa cells was used to confirm the presence of EGR1 in the nucleolus mainly as the 100 kDa sumoylated form. We also show that the level of the ribosomal RNA precursor 47S is inversely correlated to the level of EGR1 transcripts. The EGR1 iseffective to regulate the synthesis of the 47S rRNA precursor. Then we demonstrated that EGR1 binds to the Upstream Binding Factor (UBF) leading us to hypothesize that the regulating activity of EGR1 is mediated by its interaction within the transcriptional complex of RNA polymerase I. These results confirm the presence of EGR1 in the nucleolus and point to a role for EGR1 in the control of nucleolar metabolism.
Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip
Shilpi Arora, Yipeng Wang, Zhenyu Jia, Saynur Vardar-Sengul, Ayla Munawar, Kutbuddin S Doctor, Michael Birrer, Michael McClelland, Eileen Adamson, Dan Mercola
Genome Biology , 2008, DOI: 10.1186/gb-2008-9-11-r166
Abstract: UV irradiation led to significant binding of 288 gene promoters by Egr1. A major functional subgroup consisted of apoptosis related genes. The largest subgroup of 24 genes belongs to the epidermal growth factor receptor-signal transduction pathway. Egr1 promoter binding had a significant impact on gene expression of target genes. Conventional chromatin immunoprecipitation and quantitative real time PCR were used to validate promoter binding and expression changes. Small interfering RNA experiments were used to demonstrate the specific role of Egr1 in gene regulation. UV stimulation promotes growth arrest and apoptosis of M12 cells and our data clearly show that a downstream target of the epidermal growth factor receptor, namely Egr1, mediates this apoptotic response. Our study also identified numerous previously unknown targets of Egr1. These include FasL, MAX and RRAS2, which may play a role in the apoptotic response/growth arrest.Our results indicate that M12 cells undergo Egr1-dependent apoptotic response upon UV stimulation and led to the identification of downstream targets of Egr1, which mediate epidermal growth factor receptor function.Early growth response-1 (Egr1) is a zinc-finger nuclear phosphoprotein and transcription factor [1,2]. The gene for Egr1 (also known as Zif/268, NGFI-A and Knox24) encodes a 533 amino acid protein with 6 Cys2-His2 zinc finger motifs that exhibit partial homology to the gene sequence encoding the DNA binding domain of the Wilms tumor-1 suppressor (WT1) [3]. Indeed, both Egr1 and WT1 bind the Egr1 consensus regulatory sequence CGCCCCCGC in a zinc-dependent manner. Egr1 was first cloned as NGFI-A [4] from NGF-induced PC12 cells, and as Egr1 from mouse cells [1]. Early studies indicated its potential roles in cardiac and neural differentiation in a pluripotent EC (endothelial cells) line [1] and a role in monocytic differentiation of myeloid leukemia cells [5]. Subsequent studies have identified roles of Egr1 in cell growth, differ
Coordinated Sumoylation and Ubiquitination Modulate EGF Induced EGR1 Expression and Stability  [PDF]
Arcangela Gabriella Manente, Giulia Pinton, Daniela Tavian, Gerardo Lopez-Rodas, Elisa Brunelli, Laura Moro
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0025676
Abstract: Background Human early growth response-1 (EGR1) is a member of the zing-finger family of transcription factors induced by a range of molecular and environmental stimuli including epidermal growth factor (EGF). In a recently published paper we demonstrated that integrin/EGFR cross-talk was required for Egr1 expression through activation of the Erk1/2 and PI3K/Akt/Forkhead pathways. EGR1 activity and stability can be influenced by many different post-translational modifications such as acetylation, phosphorylation, ubiquitination and the recently discovered sumoylation. The aim of this work was to assess the influence of sumoylation on EGF induced Egr1 expression and/or stability. Methods We modulated the expression of proteins involved in the sumoylation process in ECV304 cells by transient transfection and evaluated Egr1 expression in response to EGF treatment at mRNA and protein levels. Results We demonstrated that in ECV304 cells Egr1 was transiently induced upon EGF treatment and a fraction of the endogenous protein was sumoylated. Moreover, SUMO-1/Ubc9 over-expression stabilized EGF induced ERK1/2 phosphorylation and increased Egr1 gene transcription. Conversely, in SUMO-1/Ubc9 transfected cells, EGR1 protein levels were strongly reduced. Data obtained from protein expression and ubiquitination analysis, in the presence of the proteasome inhibitor MG132, suggested that upon EGF stimuli EGR1 sumoylation enhanced its turnover, increasing ubiquitination and proteasome mediated degradation. Conclusions Here we demonstrate that SUMO-1 modification improving EGR1 ubiquitination is involved in the modulation of its stability upon EGF mediated induction.
武汉市城区居民癌亡率分析  [PDF]
韩荣华, 孙惠玲
中国公共卫生 , 1994,
Abstract: ?癌是危害人体健康和生命的常见病。为了解癌在人群中死亡率及其分布规律,为防癌提供科学依据,现将武汉市城区居民1980~1989年10年间的癌亡率作如下分析讨论。
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