アクチベータータンパク質1
- 関
- AP-1、transcription factor AP-1
WordNet
- any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
- (biology) any agency bringing about activation; a molecule that increases the activity of an enzyme or a protein that increases the production of a gene product in DNA transcription
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- 蛋白(たんばく)質
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English Journal
- Loss of stromal JUNB does not affect tumor growth and angiogenesis.
- Braun J, Strittmatter K, Nübel T, Komljenovic D, Sator-Schmitt M, Bäuerle T, Angel P, Schorpp-Kistner M.Author information Division of Signal Transduction and Growth Control DKFZ DKFZ-ZMBH Alliance, German Cancer Research Center (DKFZ), Heidelberg, Germany.AbstractThe transcription factor AP-1 subunit JUNB has been shown to play a pivotal role in angiogenesis. It positively controls angiogenesis by regulating Vegfa as well as the transcriptional regulator Cbfb and its target Mmp13. In line with these findings, it has been demonstrated that tumor cell-derived JUNB promotes tumor growth and angiogenesis. In contrast to JUNB's function in tumor cells, the role of host-derived stromal JUNB has not been elucidated so far. Here, we show that ablation of Junb in stromal cells including endothelial cells (ECs), vascular smooth muscle cells (SMCs) and fibroblasts does not affect tumor growth in two different syngeneic mouse models, the B16-F1 melanoma and the Lewis lung carcinoma model. In-depth analyses of the tumors revealed that tumor angiogenesis remains unaffected as assessed by measurements of the microvascular density and relative blood volume in the tumor. Furthermore, we could show that the maturation status of the tumor vasculature, analyzed by the SMC marker expression, α-smooth muscle actin and Desmin, as well as the attachment of pericytes to the endothelium, is not changed upon ablation of Junb. Taken together, these results indicate that the pro-angiogenic functions of stromal JUNB are well compensated with regard to tumor angiogenesis and tumor growth.
- International journal of cancer. Journal international du cancer.Int J Cancer.2014 Mar 15;134(6):1511-6. doi: 10.1002/ijc.28477. Epub 2013 Oct 9.
- The transcription factor AP-1 subunit JUNB has been shown to play a pivotal role in angiogenesis. It positively controls angiogenesis by regulating Vegfa as well as the transcriptional regulator Cbfb and its target Mmp13. In line with these findings, it has been demonstrated that tumor cell-derived
- PMID 24027048
- AP-1 regulates sphingosine kinase 1 expression in a positive feedback manner in glomerular mesangial cells exposed to high glucose.
- Huang K1, Huang J2, Chen C1, Hao J1, Wang S1, Huang J1, Liu P1, Huang H3.Author information 1Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.2Yunnan Baiyao Group Co. Ltd, Kunming 650500, China.3Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: huangheq@mail.sysu.edu.cn.AbstractOur previous studies have confirmed that the sphingosine kinase 1 (SphK1)-sphingosine 1-phosphate (S1P) signaling pathway in the kidney under diabetic conditions is closely correlated with the pathogenesis of diabetic nephropathy (DN). The activation of SphK1-S1P pathway by high glucose (HG) can increase the expression of fibronectin (FN), an important fibrotic component, in glomerular mesangial cells (GMCs) by promoting the DNA-binding activity of transcription factor AP-1. However, the mechanism responsible for the sustained activation of SphK1-S1P pathway remains unclear. Given the binding motifs for AP-1 within the first intron of the SphK1 gene, we speculated that the activated AP-1 in the kidney under HG condition possibly regulates SphK1 expression in a positive feedback manner, thereby promoting the sustained activation of SphK1-S1P pathway and mediating the pathological progression of DN. Here, we observed the effect of AP-1 on SphK1 expression in GMCs and explored the molecular mechanism involved in the sustained activation of SphK1-S1P pathway. We found two consensus binding motifs for AP-1 in the promoter sequences and non-coding region downstream of the transcriptional initiation of the rat SphK1 gene by chromatin immunoprecipitation assay. The treatment of GMCs with both HG and S1P significantly increased the protein expression of c-Jun and c-Fos, and obviously enhanced the phosphorylation of c-Jun at Ser63 and Ser73, and c-Fos at Ser32. Knockdown of c-Jun and c-Fos with siRNAs substantially inhibited the expression of SphK1 and FN, whereas overexpression of c-Jun and c-Fos significantly increased the expression of SphK1 and FN. Curcumin treatment greatly decreased the levels of c-Jun, c-Fos, SphK1, and FN in the kidney tissues of diabetic rats. SiRNAs targeting SphK1 and S1P2 receptor respectively inhibited the phosphorylation of c-Jun (ser63 and ser73) and c-Fos (ser32), as well as FN expression under both normal and HG conditions. Our data demonstrated that the activated SphK1-S1P signaling pathway in GMCs under diabetic conditions is closely associated with AP-1 to form a positive feedback loop. This positive feedback loop functions as an important molecular basis for the sustained activation of SphK1-S1P pathway and increased FN expression that lead to the initiation and progression of DN.
- Cellular signalling.Cell Signal.2014 Mar;26(3):629-38. doi: 10.1016/j.cellsig.2013.12.002. Epub 2013 Dec 14.
- Our previous studies have confirmed that the sphingosine kinase 1 (SphK1)-sphingosine 1-phosphate (S1P) signaling pathway in the kidney under diabetic conditions is closely correlated with the pathogenesis of diabetic nephropathy (DN). The activation of SphK1-S1P pathway by high glucose (HG) can inc
- PMID 24342046
- High glucose driven expression of pro-inflammatory cytokine and chemokine genes in lymphocytes: Molecular mechanisms of IL-17 family gene expression.
- Kumar P1, Natarajan K1, Shanmugam N2.Author information 1Department of Biomedical Science, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India.2Department of Biomedical Science, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India. Electronic address: nshanmugam@bdu.ac.in.AbstractHigh glucose is an independent risk factor that alters the expression pattern of cytokines/chemokine leading to leukocyte activation in diabetes. Fluctuation of cytokine milieu in lymphocytes may lead to differentiation into a particular subset. Our objectives were to profile high glucose induced inflammatory gene expression in lymphocytes, to examine in vivo relevance in diabetes and to identify the key transcription factors and signaling pathways involved. Cytokine gene arrays and T-helper (Th1/Th2/Th17) cytokine profiler RT(2)-PCR arrays used for cytokine expression profiling followed by validation using Real Time-qPCR and relative RT-PCR in Jurkat T-lymphocytes, peripheral blood lymphocytes (PBLCs) from normal and diabetes subjects. Luciferase reporter plasmid, pharmacological inhibitors and mutant plasmids were used for promoter activation and signaling pathway studies. High glucose induced gene profiling in Jurkat T-lymphocytes showed significantly increased expression of 64 proinflammatory genes including IL-6 and IL-17A and most of these genes were Nuclear Factor (NF)-κB and AP-1 regulated. RT(2)-PCR array results suggested the transcriptional activation of IL-17 and its downstream signaling in Jurkat T-lymphocytes upon high glucose treatment. Candidate genes like Interleukin (IL)-17A, IL-17E IL-17F and IL-6 were up-regulated in both Jurkat T-lymphocytes and PBLCs from normal and diabetes subjects. This high glucose induced cytokine expression was due to promoter activation. Pharmacology inhibitor studies showed the involvement of NF-κB, protein kinase-C, p38 Mitogen activated protein kinase; Janus activated kinase-signal transducer and activator of transcription and extracellular regulated kinase signaling pathways. Further, high glucose treatment increased the adhesion of lymphocytes to human umbilical vein endothelial cells. These results show that IL-17 cytokines are induced by high glucose via key signaling pathways leading to lymphocyte activation and relevant to the pathogenesis of diabetic complications like atherosclerosis.
- Cellular signalling.Cell Signal.2014 Mar;26(3):528-39. doi: 10.1016/j.cellsig.2013.11.031. Epub 2013 Dec 2.
- High glucose is an independent risk factor that alters the expression pattern of cytokines/chemokine leading to leukocyte activation in diabetes. Fluctuation of cytokine milieu in lymphocytes may lead to differentiation into a particular subset. Our objectives were to profile high glucose induced in
- PMID 24308966
Japanese Journal
- Advanced Glycation Endproducts Stimulate Renal Epithelial Cells to Release Chemokines That Recruit Macrophages, Leading to Renal Fibrosis
- SASAI Yosuke,IWAKAWA Kousei,YANAGIDA Kanako [他]
- Bioscience, Biotechnology, and Biochemistry 76(9), 1741-1745, 2012-09
- NAID 40019425098
- Regulatory Pathways Controlling the Endovascular Invasive Trophoblast Cell Lineage
- SOARES Michael J.,CHAKRABORTY Damayanti,RENAUD Stephen J.,KUBOTA Kaiyu,BU Pengli,KONNO Toshihiro,RUMI M. A. Karim
- The Journal of reproduction and development 58(3), 283-287, 2012-06-01
- … With these research approaches, two signaling pathways controlling the differentiation and invasion of the trophoblast cell lineage have been identified: i) hypoxia/hypoxia inducible factor and ii) phosphatidylinositol 3-kinase/AKT/Fos like antigen 1. …
- NAID 10030820970
Related Links
- Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in mouse development as well as in the whole ...
- 1. Arthritis Res Ther. 2008;10(1):201. doi: 10.1186/ar2338. Epub 2008 Jan 18. Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease. Zenz R(1), Eferl R, Scheinecker C, Redlich K, Smolen J ...
★リンクテーブル★
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- 英
- activator protein-1、AP-1
- 関
- 転写因子AP-1
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転写因子AP-1
- 関
- activator protein-1、AP-1
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