Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An augmentation of Fas antigen induced by radiation was examined using flow cytometry. Six cell lines established from lymphomas or leukemias (HD-70, FLAM-76, CML-C-1, CML-C-2, DL-40 and DL-95) were used in this study. Each cell line was distributed to two dishes. The cells in one dish were irradiated at 10 Gy with cobalt-60 gamma rays. The control cells were not irradiated. At 6 h, 24 h, and 48 h after treatment, irradiated and non-irradiated cells of each cell line were stained with fluorescein isocyanate (FITC)-conjugated anti-human Fas antibody, and analyzed with flow cytometry. Mean fluorescence intensity (MFI) values of irradiated or non-irradiated cells were examined. MFI rates (MFI value of irradiated cells/MFI value of non-irradiated cells) of each cell line were calculated at each investigated time point, and an augmentation of the Fas antigen expression with radiation was evaluated. FLAM-76 did not express Fas antigen at any time. An augmented expression of Fas antigen due to irradiation was observed in the other five cell lines. These findings strongly suggest that radiation can augment Fas antigen expression in certain tumor cells. Further studies using Fas ligand or specific anti-Fas antibody are needed.
Int J Mol Med 1999 Mar
PMID:An augmentation of Fas (CD95/APO-1) antigen induced by radiation: flow cytometry analysis of lymphoma and leukemia cell lines. 1002 51

The ubiquitin conjugating (ubc) E2 enzyme ubc-9 conjugates the ubiquitin-like peptide sentrin/SUMO-1/PIC1 to target proteins which include the Fas antigen. We show that the mouse genome contains four copies of the ubc-9 gene. These include a structural ubc-9 gene consisting of seven exons which encode a protein identical to human ubc-9, and three intronless processed pseudogenes. The open reading frames (ORF) of two of the pseudogenes, ubc9-psi1 and ubc9-psi2, correspond to the cDNA of ubc-9 and encode for proteins which differ from ubc9 by three and one amino acid substitutions respectively. The third pseudogene, ubc9-psi3, contains many mutations and stop codons. ubc9-psi1 and ubc9-psi2 are flanked by 5'- and 3'-untranslated (UT) regions homologous to those of the structural ubc-9 gene. Both genes contain a polyA tail and direct repeats at both ends suggesting that they arose by mRNA retroposition. Both ubc9-psi1 and ubc9-psi2 are transcribed into mRNA in murine cells. In contrast to ubc9, the protein products of ubc9-psil and ubc9-psi2 fail to bind Fas and to complement an yeast conditional ubc9 mutant. These results suggest that ubc9-psi1 and ubc9-psi2 encode for proteins that may interact with targets that differ from those recognized by ubc-9.
Mol Immunol 1998 Nov
PMID:The mouse genome contains two expressed intronless retroposed pseudogenes for the sentrin/sumo-1/PIC1 conjugating enzyme Ubc9. 1006 40

Several cardioprotective proteins are induced during myocardial ischemia, such as heat shock proteins and anti-apoptotic Bcl-2-related proteins which, when experimentally overexpressed, have been shown to prevent ischemia-induced myocyte loss. As this pathophysiological induction is obviously not sufficient to prevent losses of myocytes, we analysed whether it could occur under moderate myocardial ischemia with hibernation, thus potentially contributing to myocyte protection under these conditions. Therefore, using anesthetized pigs with documented myocardial hypoperfusion and short-term hibernation, we investigated the left ventricular mRNA expression of the inducible heat shock protein Hsp70 and of the anti-apoptotic Bcl-XL in comparison with the pro-apoptotic Bak and Fas expression. For transcriptional analyses, the porcine cDNA sequences of Bcl-XL, Bak and Fas were identified by polymerase chain reaction (PCR) or by screening of a porcine heart cDNA library and cloned. Using reverse transcription polymerase chain reaction (RT-PCR), we observed an unchanged mRNA expression of inducible Hsp70, Bcl-XL, Bak and Fas after 85 min of hypoperfusion in the short-term hibernating myocardium, as well as after 30 min of subsequent reperfusion in the stunned myocardium, compared with transcription in a non-hypoperfused control area of the same ventricle. In conclusion, the mRNA expression of inducible Hsp70 and of several apoptosis-modulating proteins is not altered during moderate myocardial ischemia resulting in short-term hibernation of the affected area and during subsequent stunning.
J Mol Cell Cardiol 1999 Jan
PMID:Quantification of cardioprotective gene expression in porcine short-term hibernating myocardium. 1007 23

Protein kinase CK2 is a ubiquitous, highly conserved protein kinase with a tetrameric alpha2beta2 structure. For the formation of this tetrameric complex a beta-alpha dimer seems to be a prerequisite. Using the two-hybrid system and a series of CK2beta deletion mutants, we mapped domains involved in alpha-beta and beta-beta interactions. We also detected an intramolecular beta interaction within the amino acid stretch 132-165. Using CK2beta as a bait in a two-hybrid library screening several new putative cellular partners have been identified, among them the S6 kinase p90rsk, the putative tumor suppressor protein Doc-1, the Fas-associated protein FAF1, the mitochondrial translational initiation factor 2 and propionyl CoA carboxylase beta subunit.
Mol Cell Biochem 1999 Jan
PMID:Interactions of protein kinase CK2beta subunit within the holoenzyme and with other proteins. 1009 92

The tumor necrosis factor receptor, p60 (TNF-R1), transduces death signals via the association of its cytoplasmic domain with several intracellular proteins. By screening a mammalian cDNA library using the yeast two-hybrid cloning technique, we isolated a ubiquitin-homology protein, DAP-1, which specifically interacts with the cytoplasmic death domain of TNF-R1. Sequence analysis reveals that DAP-1 shares striking sequence homology with the yeast SMT3 protein that is essential for the maintenance of chromosome integrity during mitosis (Meluh, P. B., and Koshland, D. (1995) Mol. Biol. Cell 6, 793-807). DAP-1 is nearly identical to PIC1, a protein that interacts with the PML tumor suppressor implicated in acute promyelocytic leukemia (Boddy, M. N., Howe, K., Etkin, L. D., Solomon, E., and Freemont, P. S. (1996) Oncogene 13, 971-982), and the sentrin protein, which associates with the Fas death receptor (Okura, T., Gong, L., Kamitani, T., Wada, T., Okura, I., Wei, C. F., Chang, H. M., and Yeh, E. T. (1996) J. Immunol. 157, 4277-4281). The in vivo interaction between DAP-1 and TNF-R1 was further confirmed in mammalian cells. In transient transfection assays, overexpression of DAP-1 suppresses NF-kappaB/Rel activity in 293T cells, a human kidney embryonic carcinoma cell line. Overexpression of either DAP-1 or sentrin causes apoptosis of TNF-sensitive L929 fibroblast cell line, as well as TNF-resistant osteosarcoma cell line, U2OS. Furthermore, the dominant negative Fas-associated death domain protein (FADD) protein blocks the cell death induced by either DAP-1 or FADD. Collectively, these observations highly suggest a role for DAP-1 in mediating TNF-induced cell death signaling pathways, presumably through the recruitment of FADD death effector.
 ...
PMID:The ubiquitin-homology protein, DAP-1, associates with tumor necrosis factor receptor (p60) death domain and induces apoptosis. 1018 98

The monolayer of endothelial cells that coats the luminal surface of the vessel wall has numerous physiological functions, including the prevention of coagulation, control of vascular permeability, maintenance of vascular tone and regulation of leukocyte extravasation. Recently, we detected functional Fas ligand (FasL) expression on the endothelial lining of blood vessels. FasL induces apoptotic cell death in the multitude of cell types that express its receptor, Fas. Here, we review the function of vascular endothelium in controlling leukocyte extravasation, and illustrate how the regulation of endothelial FasL expression might contribute to this process. We also describe the role of leukocyte extravasation in angiogenesis and atherosclerosis, and we suggest that FasL gene transfer might provide a means of treating diseases of the proliferative vessel wall, particularly those that result from the detrimental infiltration of inflammatory cells.
Mol Med Today 1999 Feb
PMID:Is extravasation a Fas-regulated process? 1020 Sep 46

Recent work suggests a participation of mitochondria in apoptotic cell death. This role includes the release of apoptogenic molecules into the cytosol preceding or after a loss of mitochondrial membrane potential DeltaPsim. The two uncouplers of oxidative phosphorylation carbonyl cyanide m-chlorophenylhydrazone (CCCP) and 2, 4-dinitrophenol (DNP) reduce DeltaPsim by direct attack of the proton gradient across the inner mitochondrial membrane. Here we show that both compounds enhance the apoptosis-inducing capacity of Fas/APO-1/CD95 signaling in Jurkat and CEM cells without causing apoptotic changes on their own account. This amplification occurred upstream or at the level of caspases and was not inhibited by Bcl-2. The effect could be blocked by the cowpox protein CrmA and is thus likely to require caspase 8 activity. Apoptosis induction by staurosporine in Jurkat cells as well as by Fas in SKW6 cells was unaffected by CCCP and DNP. The role of cytochrome c during Fas-DNP signaling was investigated. No early cytochrome c release from mitochondria was detected by Western blotting. Functional assays with cytoplasmic preparations from Fas-DNP-treated cells also indicated that there was no major contribution by cytochrome c or caspase 9 to the activation of effector caspases. Furthermore, an increase of rhodamine-123 uptake into intact cells, which has been explained by mitochondrial swelling, occurred considerably later than the caspase activation and was blocked by Z-VAD-fmk. These data show that uncouplers of oxidative phosphorylation can presensitize some but not all cells for a Fas death signal and provide information about the existence of separate pathways in the induction of apoptosis.
Mol Cell Biol 1999 May
PMID:Uncouplers of oxidative phosphorylation can enhance a Fas death signal. 1020 55

Death receptor Fas transduces cell death signaling upon stimulation by Fas ligand, and this death signaling is mediated by caspase. Recently, we reported that the cell cycle regulator p21 interacts with procaspase 3 to resist Fas-mediated cell death. In the present study, the molecular characterization and functional region of the procaspase 3-p21 complex was further investigated. We observed the p21 expression in the mitochondrial fraction of HepG2 cells and detected Fas-mediated cell death only in the presence of actinomycin D. However, mitochondrial-DNA-lacking HepG2 (MDLH) cells showed this effect even in the absence of actinomycin D. Both p21 and procaspase 3 were expressed in MDLH cells, but the procaspase 3-p21 complex formation was not observed. Interestingly, the resistance to Fas-mediated cell death in the MDLH cells without actinomycin D was recovered after microinjection of HepG2-derived mitochondria into the MDLH cells. We conclude that mitochondria are necessary for procaspase 3-p21 complex formation and propose that the mitochondrial role during cell death is not only death induction but also death suppression.
Mol Cell Biol 1999 May
PMID:Mitochondrial regulation of cell death: mitochondria are essential for procaspase 3-p21 complex formation to resist Fas-mediated cell death. 1020 7

CD8(+) T cells appear to play an important pathophysiologic role in many inflammatory lung diseases. The primary effector function of this T-cell subset is cytolysis of virus-infected cells, and it is widely believed that there are two primary molecular mechanisms by which this occurs: the perforin/granzyme-mediated pathway of cytolysis, and the Fas ligand (FasL)-Fas (CD95/APO-1) pathway of induction of target-cell apoptosis. This conclusion is based primarily on data obtained with hematopoetic cell lines as target cells. There is also a growing body of evidence that Fas is involved in the transduction of apoptotic signals in a variety of inflammatory disease states, particularly involving the liver and the lung. In the study reported here we took advantage of a novel in vitro assay to directly assess the effector mechanisms employed in CD8(+) T-cell-mediated cytolysis of alveolar epithelial cells. We present evidence that FasL-induced, Fas-mediated apoptosis does not directly contribute to T-cell-mediated cytolysis of alveolar epithelial-derived cells, even though Fas is expressed and functional on these cells. We also demonstrated that the perforin-independent cytolytic activity of CD8(+) T cells against alveolar epithelial-derived cells is explained entirely by tumor necrosis factor-alpha (TNF-alpha), which is expressed on CD8(+) T cells. Furthermore, we show that bystander cytolysis of alveolar epithelial-derived cells by antiviral CD8(+) T cells is entirely perforin-independent. This activity is mediated exclusively by TNF-alpha. Both alveolar epithelial-derived cells and primary murine type II cells show susceptibility to apoptosis triggered by soluble TNF-alpha, without the need for transcriptional or translational inhibition. We also confirmed the resistance of alveolar type II cells to FasL in vivo by performing adoptive transfer of perforin-deficient antiviral CD8(+) T cells into transgenic mice expressing a target antigen in type II epithelial cells. Significant lung injury developed in the transgenic CD8(+) T-cell recipients, whether or not Fas was expressed in these animals. Furthermore, preincubation of the T cells with antibody to TNF-alpha completely abolished the injury. These results suggest that alveolar epithelial cells are relatively sensitive to T cell-triggered, TNF-alpha-mediated apoptosis, and resistant to apoptosis triggered by FasL. These observations may have important ramifications for understanding of the pathophysiology of interstitial and inflammatory lung diseases.
Am J Respir Cell Mol Biol 1999 May
PMID:Perforin-independent CD8(+) T-cell-mediated cytotoxicity of alveolar epithelial cells is preferentially mediated by tumor necrosis factor-alpha: relative insensitivity to Fas ligand. 1022 53

In this study, we investigate Fas ligand expression in the human endometrium during the menstrual cycle in relation to Fas antigen and Bcl-2 expression, using immunoelectron microscopy and Western blotting. Endometrial samples were obtained from 54 pre-menopausal non-pregnant women who underwent laparotomies for benign diseases. The Fas ligand, as well as the Fas antigen, were expressed on the surface of endometrial glandular cells throughout the menstrual cycle, whereas Bcl-2 showed a cyclic expression pattern, peaking during the late proliferative phase. A noteworthy finding was that both the Fas ligand and the Fas antigen were localized on Golgi apparatuses and vesicles, in addition to the cell membranes, during the late proliferative phase. These results indicate that the Fas ligand and Fas antigen which are localized on Golgi apparatus and vesicles during the late proliferative phase are incorporated into the cell membranes during the secretory phase, and are co-expressed on the cell membranes of endometrial glands throughout the menstrual cycle. The factors regulating Fas-mediated apoptosis in the human endometrium, including the level of expression of the Fas ligand and Bcl-2 are discussed.
Mol Hum Reprod 1999 Apr
PMID:Fas ligand, Fas antigen and Bcl-2 expression in human endometrium during the menstrual cycle. 1032 8


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>