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https://www.readbyqxmd.com/read/28728983/etv4-and-ap1-transcription-factors-form-multivalent-interactions-with-three-sites-on-the-med25-activator-interacting-domain
#1
Simon L Currie, Jedediah J Doane, Kathryn S Evans, Niraja Bhachech, Bethany J Madison, Desmond K W Lau, Lawrence P McIntosh, Jack J Skalicky, Kathleen A Clark, Barbara J Graves
The recruitment of transcriptional cofactors by sequence-specific transcription factors challenges the basis of high affinity and selective interactions. Extending previous studies that the N-terminal activation domain (AD) of ETV5 interacts with Mediator subunit 25 (MED25), we establish that similar, aromatic-rich motifs located both in the AD and in the DNA-binding domain (DBD) of the related ETS factor ETV4 interact with MED25. These ETV4 regions bind MED25 independently, display distinct kinetics, and combine to contribute to a high-affinity interaction of full-length ETV4 with MED25...
July 17, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28728022/loss-of-tmem106b-ameliorates-lysosomal-and-frontotemporal-dementia-related-phenotypes-in-progranulin-deficient-mice
#2
Zoe A Klein, Hideyuki Takahashi, Mengxiao Ma, Massimiliano Stagi, Melissa Zhou, TuKiet T Lam, Stephen M Strittmatter
Progranulin (GRN) and TMEM106B are associated with several common neurodegenerative disorders including frontotemporal lobar degeneration (FTLD). A TMEM106B variant modifies GRN-associated FTLD risk. However, their functional relationship in vivo and the mechanisms underlying the risk modification remain unclear. Here, using transcriptomic and proteomic analyses with Grn(-/-) and Tmem106b(-/-) mice, we show that, while multiple lysosomal enzymes are increased in Grn(-/-) brain at both transcriptional and protein levels, TMEM106B deficiency causes reduction in several lysosomal enzymes...
July 19, 2017: Neuron
https://www.readbyqxmd.com/read/28716897/mcpip1-downregulation-in-clear-cell-renal-cell-carcinoma-promotes-vascularization-and-metastatic-progression
#3
Paulina Marona, Judyta Górka, Zofia Mazurek, Waclaw Wilk, Janusz Rys, Marcin Majka, Jolanta Jura, Katarzyna Miekus
<p>Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer and it forms highly vascularized tumors. The monocyte endoribonuclease MCPIP1 negatively regulates inflammation by degrading mRNA encoding proinflammatory cytokines, such as IL-6, IL-1 and IL-12. MCPIP1 is also a negative regulator of NFκB and AP1 activity and it influences a broad range of miRNA activities. Here we report that MCPIP1 protein levels are decreased during renal cancer progression. In patient-derived tumors, and xenografts established in NOD-SCID or nude mice, low MCPIP1 levels correlated strongly with increased proliferation, tumor outgrowth and vascularity...
July 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28711499/inhibition-of-il-6-stat3-signaling-in-human-cancer-cells-using-evista
#4
Wei Shi, Dan Yan, Chongqiang Zhao, Miaomiao Xiao, Yina Wang, Haiyan Ma, Tianshu Liu, Hua Qin, Cuntai Zhang, Chenglong Li, Jiayuh Lin, Sheng Li, Jiagao Lv, Li Lin
Persistent activation of IL-6/STAT3 signaling pathway has been frequently detected in human cancer including breast cancer, colon cancer and multiple myeloma. IL-6/STAT3 can be a promising target for cancer prevent and treatment. However, few STAT3 inhibitors with high efficiency, specificity and safety is available for present clinical cancer therapy. Evista (Raloxifene·HCl) is known as selective estrogen receptor modulator which has been used for the prevention and treatment of osteoporosis and was approved for reducing the risk of invasive breast cancer...
July 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28678424/the-metabolic-syndrome-alters-the-mirna-signature-of-porcine-adipose-tissue-derived-mesenchymal-stem-cells
#5
Yu Meng, Alfonso Eirin, Xiang-Yang Zhu, Hui Tang, Pritha Chanana, Amir Lerman, Andre J Van Wijnen, Lilach O Lerman
Autologous transplantation of mesenchymal stem cells (MSCs) is a viable option for the treatment of several diseases. Evidence indicates that MSCs release extracellular vesicles (EVs) and that EVs shuttle miRNAs to damaged parenchymal cells to activate an endogenous repair program. We hypothesize that comorbidities may interfere with the packaging of cargo in MSC-derived EVs. Therefore, we examined whether metabolic syndrome (MetS) modulates the miRNA content packed within MSC-derived EVs. MSCs were collected from swine abdominal adipose tissue after 16 weeks of lean or obese diet (n = 7 each)...
July 5, 2017: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/28627437/molecular-characterization-and-functional-analysis-of-ppar%C3%AE-promoter-in-yellow-catfish-pelteobagrus-fulvidraco
#6
Wen-Jing You, Yao-Fang Fan, Yi-Huan Xu, Kun Wu, Xiao-Ying Tan
Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor that plays critical roles in the regulation of many important physiological processes. In the present study, the 1686-bp PPARα promoter for yellow catfish Pelteobagrus fulvidraco was first cloned and characterized. The transcription start site (TSS) of PPARα gene was mapped using RLM-5'RACE method. The luciferase vectors were constructed and transiently transfected into HepG2 cells and HEK293 cells, respectively, for functional analysis of promoters...
June 13, 2017: Gene
https://www.readbyqxmd.com/read/28620147/prostaglandin-i2-is-responsible-for-ameliorating-prostaglandin-e2-stress-in-stimulating-the-expression-of-tumor-necrosis-factor-%C3%AE-in-a-%C3%AE-amyloid-protein-dependent-mechanism
#7
Shao-Qin Zheng, Zi-Yi Gong, Chen-Di Lu, Pu Wang
Cyclooxygenase-2 (COX-2) has been found to be induced during the early stage of Alzheimer's disease (AD). Using mouse-derived astrocyte and APP/PS1 transgenic (Tg) mice as model systems, we firstly elucidated the mechanisms underlying COX-2 metabolic production including prostaglandin (PG)E2- and PGI2-mediated tumor necrosis factor α (TNF-α) regulation. Specifically, PGE2 accumulation in astrocyte activated the p38 and JNK/c-Jun signaling pathways via phosphorylation, resulting in TNF-α expression. In contrast, the administration of PGI2 attenuated the effects of PGE2 in stimulating the production of TNF-α by inhibiting the activity of TNF-α promoter and the binding activity of AP1 on the promoter of TNF-α...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611810/evolutionary-analysis-of-mikc-c-type-mads-box-genes-in-gymnosperms-and-angiosperms
#8
Fei Chen, Xingtan Zhang, Xing Liu, Liangsheng Zhang
MIKC(c)-type MADS-box genes encode transcription factors that control floral organ morphogenesis and flowering time in flowering plants. Here, in order to determine when the subfamilies of MIKC(c) originated and their early evolutionary trajectory, we sampled and analyzed the genomes and large-scale transcriptomes representing all the orders of gymnosperms and basal angiosperms. Through phylogenetic inference, the MIKC(c)-type MADS-box genes were subdivided into 14 monophyletic clades. Among them, the gymnosperm orthologs of AGL6, SEP, AP1, GMADS, SOC1, AGL32, AP3/PI, SVP, AGL15, ANR1, and AG were identified...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28585919/transcriptional-networks-specifying-homeostatic-and-inflammatory-programs-of-gene-expression-in-human-aortic-endothelial-cells
#9
Nicholas T Hogan, Michael B Whalen, Lindsey K Stolze, Nizar K Hadeli, Michael T Lam, James R Springstead, Christopher K Glass, Casey E Romanoski
Endothelial cells (ECs) are critical determinants of vascular homeostasis and inflammation, but transcriptional mechanisms specifying their identities and functional states remain poorly understood. Here, we report a genome-wide assessment of regulatory landscapes of primary human aortic endothelial cells (HAECs) under basal and activated conditions, enabling inference of transcription factor networks that direct homeostatic and pro-inflammatory programs. We demonstrate that 43% of detected enhancers are EC-specific and contain SNPs associated to cardiovascular disease and hypertension...
June 6, 2017: ELife
https://www.readbyqxmd.com/read/28585201/the-pathogenesis-of-obesity-associated-adipose-tissue-inflammation
#10
Atilla Engin
Obesity is characterized by a state of chronic, low-grade inflammation. However, excessive fatty acid release may worsen adipose tissue inflammation and contributes to insulin resistance. In this case, several novel and highly active molecules are released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines. Most likely cytokines that are released by inflammatory cells infiltrating obese adipose tissue are such as tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1) (CCL-2) and IL-1...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28569792/loss-of-epidermal-ap1-transcription-factor-function-reduces-filaggrin-level-alters-chemokine-expression-and-produces-an-ichthyosis-related-phenotype
#11
Christina A Young, Ellen A Rorke, Gautam Adhikary, Wen Xu, Richard L Eckert
AP1 transcription factors are important controllers of epidermal differentiation. Multiple family members are expressed in the epidermis in a differentiation-dependent manner, where they function to regulate gene expression. To study the role of AP1 factor signaling, TAM67 (dominant-negative c-jun) was inducibly expressed in the suprabasal epidermis. The TAM67-positive epidermis displays keratinocyte hyperproliferation, hyperkeratosis and parakeratosis, delayed differentiation, extensive subdermal vasodilation, nuclear loricrin localization, tail and digit pseudoainhum and reduced filaggrin level...
June 1, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28546125/molecular-cloning-and-functional-characterization-of-coft1-a-homolog-of-flowering-locus-t-ft-from-camellia-oleifera
#12
Hengjiu Lei, Shuchai Su, Luyi Ma, Yue Wen, Xiangnan Wang
FLOWERING LOCUS T (FT) is an important integrator of flowering genetic pathways and plays crucial roles in flowering transition. The tea-oil tree (Camellia oleifera Abel.) is a valuable woody oil crop, but the molecular mechanisms controlling flowering are still unclear. In this study, a FT-like gene, CoFT1, was isolated and characterized from C. oleifera. The CoFT1 protein was localized in the nucleus and cytoplasm of Arabidopsis protoplasts, and exhibited no transactivation activity in yeast cells. CoFT1 was highly expressed in mature leaves and reproductive organs, such as flower buds, flowers, flower organs, and young fruits...
May 22, 2017: Gene
https://www.readbyqxmd.com/read/28538192/hepatic-anti-inflammatory-effect-of-hexane-extracts-of-dioscorea-batatas-decne-possible-suppression-of-toll-like-receptor-4-mediated-signaling
#13
Hyun Jung Koo, SungRyul Lee, Kwang Jin Chang, Eunsoo Sohn, Eun-Hwa Sohn, Se Chan Kang, Suhkneung Pyo
The hepatic anti-inflammatory potential of hexane extracts of Dioscorea batatas Decne edible part (EDH-1e) and bark (EDH-2b) were investigated in Western-type diet-fed apolipoprotein E null [ApoE (-/-)] mice and HepG2 cells. EDH-1e and EDH-2b suppressed the increased levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, transforming growth factor beta 1 (TGF-β1), vascular cell adhesion protein 1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), and reduced infiltration of monocytes into liver tissue...
August 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28528978/multimodal-control-of-transcription-factor-pap1-in-schizosaccharomyces-pombe-under-nitrosative-stress
#14
Puranjoy Kar, Pranjal Biswas, Sanjay Ghosh
Schizosaccharomyces pombe Pap1, a bZIP transcription factor, is highly homologous to the mammalian c-Jun protein that belongs to the AP1 family of transcriptional regulators. The role of transcription factor Pap1 has been extensively studied under oxidative stress. Two cysteine residues in Pap1p namely, C278 and C501 form disulfide linkage under oxidative stress resulting in nuclear accumulation. We first time showed the involvement of Pap1 in the protection against nitrosative stress. In the present study we show that pap1 deletion makes growth of S...
July 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28528205/heterotrimeric-complex-of-p38-mapk-pkc%C3%AE-and-tirap-is-required-for-ap1-mediated-inflammatory-response
#15
Mirza S Baig, Dongfang Liu, Kannan Muthu, Anjali Roy, Uzma Saqib, Adnan Naim, Syed M Faisal, Mansi Srivastava, Rohit Saluja
Inflammation could be described as a physiological response of the body to tissue injury, pathogen invasion, and irritants. During the inflammatory phase, cells of both the innate as well as adaptive immune system are activated and recruited to the site of inflammation. These mediators are downstream targets for the transcription factors; activator protein-1 (AP1), nuclear factor kappa-light-chain-enhancer (NF-κB), signal transducers and activators of transcription factors (STAT1), as well as interferon regulatory factors (IRFs), which control the expression of most immunomodulatory genes...
May 18, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28526300/embryonic-ap1-transcription-factor-deficiency-causes-a-collodion-baby-like-phenotype
#16
Christina A Young, Richard L Eckert, Gautam Adhikary, Debra Crumrine, Peter M Elias, Miroslav Blumenberg, Ellen A Rorke
AP1 transcription factors are important controllers of gene expression in the epidermis, and altered AP1 factor function can perturb keratinocyte proliferation and differentiation. However, our understanding of how AP1 signaling changes may underlie or exacerbate skin disease is limited. We have shown that inhibiting AP1 factor function in suprabasal adult epidermis leads to reduced filaggrin levels and to a phenotype that resembles the genetic disorder, ichthyosis vulgaris. We now show that inhibiting AP1 factor function during development in embryonic epidermis produces marked phenotypic changes including reduced filaggrin mRNA and protein levels, compromised barrier function, marked ultrastructural change and enhanced dehydration susceptibility that resembles the phenotype observed in the flaky tail mouse, a model for ichthyosis vulgaris...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28515730/analysis-of-mads-box-gene-family-reveals-conservation-in-floral-organ-abcde-model-of-moso-bamboo-phyllostachys-edulis
#17
Zhanchao Cheng, Wei Ge, Long Li, Dan Hou, Yanjun Ma, Jun Liu, Qingsong Bai, Xueping Li, Shaohua Mu, Jian Gao
Mini chromosome maintenance 1, agamous, deficiens, and serum response factor (MADS)-box genes are transcription factors which play fundamental roles in flower development and regulation of floral organ identity. However, till date, identification and functions of MADS-box genes remain largely unclear in Phyllostachys edulis. In view of this, we performed a whole-genome survey and identified 34 MADS-box genes in P. edulis, and based on phylogeny, they were classified as MIKC(C), MIKC(∗), Mα, and Mβ. The detailed analysis about gene structure and motifs, phylogenetic classification, comparison of gene divergence and duplication are provided...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28492344/andrographis-paniculata-diterpenoids-protect-against-radiation-induced-transformation-in-balb-3t3-cells
#18
Danupon Nantajit, Suwimol Jetawattana, Tawit Suriyo, David J Grdina, Jutamaad Satayavivad
One of the most concerning side effects of exposure to radiation are the carcinogenic risks. To reduce the negative effects of radiation, both cytoprotective and radioprotective agents have been developed. However, little is known regarding their potential for suppressing carcinogenesis. Andrographis paniculata , a plant, with multiple medicinal uses that is commonly used in traditional medicine, has three major constituents known to have cellular antioxidant activity: andrographolide (AP1); 14-deoxy-11,12-didehydroandrographolide (AP3); and neoandrographolide (AP4)...
July 2017: Radiation Research
https://www.readbyqxmd.com/read/28482915/dr5-suppression-induces-sphingosine-1-phosphate-dependent-traf2-polyubiquitination-leading-to-activation-of-jnk-ap-1-and-promotion-of-cancer-cell-invasion
#19
You-Take Oh, Ping Yue, Shi-Yong Sun
BACKGROUND: Death receptor (DR5), a well-characterized death domain-containing cell surface pro-apoptotic protein, has been suggested to suppress cancer cell invasion and metastasis. However, the underlying mechanisms have not been fully elucidated. Our recent work demonstrates that DR5 suppression promotes cancer cell invasion and metastasis through caspase-8/TRAF2-mediated activation of ERK and JNK signaling and MMP1 elevation. The current study aimed at addressing the mechanism through which TRAF2 is activated in a caspase-8 dependent manner...
May 8, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28475877/joining-forces-bmi1-inhibition-and-cisplatin-curb-squamous-carcinogenesis
#20
Jessie A Brown, Markus Schober
Head and neck squamous cell carcinomas (HNSCCs) are refractory to therapeutic interventions. Chen et al. (2017) show that mouse and human HNSCCs and their metastases depend on Bmi1-expressing cancer stem cells and AP1 signaling and that simultaneously inhibiting Bmi1 or AP1, combined with Cisplatin, reduces tumor growth effectively in preclinical models.
May 4, 2017: Cell Stem Cell
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