TY  - JOUR
A1  - Maurer, Bernd
A1  - Serfling, Edgar
A1  - ter Meulen, Volker
A1  - Rethwilm, Axel
T1  - Transcription factor AP-1 modulates the activity of the human foamy virus long terminal repeat
N2  - The human foamy virus (HFV) contains within the UJ region of its long terminal repeat (L TR) three perfect consensus sequences for the binding of the inducible transcription factor AP-1. Results of DNase I footprint protection and gel retardation assays demonstrated that proteins in extracts of HeLa and BHK-21 cells as weil as bacterially expressed Jun and Fos proteins bind to these AP-1 sites. By conducting transient expression assays using chloramphenicol acetyltransferase plasmids carrying LTR sequences with point-mutated AP-1 sites it was found that the three AP-1 sites contribute to the optimal activity ofthe HFV promoter. It is shown that lnduction of the HFV L TR by 12-O-tetradecanoylphorbol-13-acetate (TPA) and serum factors is mediated through the AP-1 sites.
KW  - Virologie
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-61444
ER  - 
TY  - JOUR
A1  - Brabletz, Thomas
A1  - Pfeuffer, Isolde
A1  - Schorr, Elke
A1  - Siebelt, Friederike
A1  - Wirth, Thomas
A1  - Serfling, Edgar
T1  - Transforming growth factor \(\beta\) and cyclosporin A inhibit the inducible activity of the interleukin-2 gene in T cells through a noncanonical octamer-binding site
N2  - Transforming growth factor \(\beta\) (TGF-\(\beta\)) has a growth-inhibitory effect on numerous different cell types of the immune system, including T lymphocytes. We show in this study that the inhibitory action of TGF-\(\beta\) on T lymphocytes is accompanied by a block of interleukin 2 (IL-2) gene expression which is mediated, at least in part, by inhibition of IL-2 promoter/enhancer activity. The functional analysis of cis-regulatory (protoenhancer) elements of the IL-2 enhancer/promoter region showed that the most TGF-\(\beta\)-responsive element maps to its so-called upstream promoter site. The proto-enhancer activity of the upstream promoter site element is also inhibited by cyclosporin A. The upstream promoter site DNA harbors two noncanonical, closely linked binding sequences for octamer and AP-1-like factors. Both sites are involved in the establishment of IL-2 enhancer activity. Since the activity of genuine octamer sites but not that of AP-1-binding sites is also impaired by TGF-\(\beta\) and cyclosporin A in E14 T lymphoma cells, we conclude that both immunosuppressives interfere with the activity but not the DNA binding of octamer factors in T lymphocytes.
Y1  - 1993
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31199
ER  - 
TY  - JOUR
A1  - Klein-Hessling, Stefan
A1  - Muhammad, Khalid
A1  - Klein, Matthias
A1  - Pusch, Tobias
A1  - Rudolf, Ronald
A1  - Flöter, Jessica
A1  - Qureischi, Musga
A1  - Beilhack, Andreas
A1  - Vaeth, Martin
A1  - Kummerow, Carsten
A1  - Backes, Christian
A1  - Schoppmeyer, Rouven
A1  - Hahn, Ulrike
A1  - Hoth, Markus
A1  - Bopp, Tobias
A1  - Berberich-Siebelt, Friederike
A1  - Patra, Amiya
A1  - Avots, Andris
A1  - Müller, Nora
A1  - Schulze, Almut
A1  - Serfling, Edgar
T1  - NFATc1 controls the cytotoxicity of CD8\(^{+}\) T cells
JF  - Nature Communications
N2  - Cytotoxic T lymphocytes are effector CD8\(^{+}\) T cells that eradicate infected and malignant cells. Here we show that the transcription factor NFATc1 controls the cytotoxicity of mouse cytotoxic T lymphocytes. Activation of Nfatc1\(^{-/-}\) cytotoxic T lymphocytes showed a defective cytoskeleton organization and recruitment of cytosolic organelles to immunological synapses. These cells have reduced cytotoxicity against tumor cells, and mice with NFATc1-deficient T cells are defective in controlling Listeria infection. Transcriptome analysis shows diminished RNA levels of numerous genes in Nfatc1\(^{-/-}\) CD8\(^{+}\) T cells, including Tbx21, Gzmb and genes encoding cytokines and chemokines, and genes controlling glycolysis. Nfatc1\(^{-/-}\), but not Nfatc2\(^{-/-}\) CD8\(^{+}\) T cells have an impaired metabolic switch to glycolysis, which can be restored by IL-2. Genome-wide ChIP-seq shows that NFATc1 binds many genes that control cytotoxic T lymphocyte activity. Together these data indicate that NFATc1 is an important regulator of cytotoxic T lymphocyte effector functions.
KW  - cytotoxic T cells
KW  - lymphocyte activation
KW  - signal transduction
KW  - gene regulation
KW  - immune cells
KW  - NFATc1
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170353
VL  - 8
IS  - 511
ER  -