Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

mRNA expression of Fas (CD95)-associated proteins [Fas-associating protein with death domain (FADD), receptor-interacting protein (RIP), and Fas-associated phosphatase-1 (FAP-1)] has been investigated in 26 Fas-positive human leukaemia/lymphoma cell lines. Reverse transcriptase-polymerase chain reaction analysis revealed that FADD and RIP mRNA were invariably expressed in both Fas-sensitive and Fas-insensitive cell lines. However, FAP-1 mRNA was detected in only 11 of 26 cell lines. Interestingly 7/14 cell lines in the Fas-sensitive group were positive for FAP-1 mRNA expression. 8/12 cell lines in the Fas-refractory group did not express FAP-1 mRNA, but half of these cell lines were susceptible to tumour necrosis factor alpha-induced growth inhibition. These findings suggest that the presence or absence of FAP-1 mRNA expression did not always correlate with relative sensitivity of Fas-mediated growth inhibition. Furthermore, it is assumed that leukaemia/lymphoma cells could possess structural or functional defects of Fas or Fas-associated proteins resulting in the failure to trigger apoptotic cell death.
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PMID:mRNA expression of Fas receptor (CD95)-associated proteins (Fas-associated phosphatase-1/FAP-1, Fas-associating protein with death domain/FADD, and receptor-interacting protein/RIP) in human leukaemia/lymphoma cell lines. 937 49

Fas transduces apoptotic signals upon cross-linking with the Fas ligand (FasL), which is experimentally replaced by agonistic anti-Fas monoclonal antibodies (mAb). Of eight human malignant hematopoietic cell lines (HL-60, KG-1, THP-1, K562, U937, Jurkat, IM-9, RPMI-8226) examined by flow cytometric analysis, all, except K562, were found to be positive for surface Fas antigen. However, despite surface Fas expression, the agonistic anti-Fas mAb (7C11) induced apoptosis in only three of seven Fas-expressing cell lines (KG-1, Jurkat and IM-9). This Fas-resistance did not correlated with high levels of mRNA either for DcR3, a decoy receptor for FasL, or for FAP-1, a Fas-associated phosphatase that can block the apoptotic function of Fas. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis did not show consistent differences in the expression of Bcl-2 and Bax between Fas-sensitive and Fas-resistant cell lines examined. These findings indicated that the presence or absence of mRNA expression of DcR3, FAP-1, Bcl-2 and Bax did not always correlate with relative sensitivity to Fas-mediated apoptosis. Treatment of cells with cycloheximide converted the phenotype of resistant cell lines from Fas-resistant to Fas-sensitive, and enhanced the sensitivity of Fas-sensitive cell lines. These results suggest that the Fas-resistance is dependent on the presence of labile proteins that determine resistance to Fas-mediated apoptosis and the apoptotic machinery is already in place in Fas-resistant cell lines.
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PMID:Fas-mediated apoptosis and expression of related genes in human malignant hematopoietic cells. 1119 Feb 79

The aim of this study was to test the hypothesis that transferrin (Tf) has anti-apoptotic properties and thereby exerts a cytoprotective effect against tissue damage induced by irradiation and other cytotoxic modalities. This hypothesis was tested in several models, including in vitro human short-term marrow cultures, subpopulations of marrow cells, particularly, CD56(+) natural killer cells (and natural killer cell lines), and in vivo radioprotection of murine marrow cells. Reverse transcriptase polymerase chain reaction analysis was used for determination of cytokine mRNA. Preincubation of human marrow with Tf protected cells (except for a CD56(+) subpopulation) against cell death induced by gamma-irradiation, tumor necrosis factor-alpha (TNF-alpha), and agonistic anti-Fas monoclonal antibody. Deglycosylation of Tf abrogated this action of Tf; conversely, Tf-derived glycans (Tf-Gly) (but not glycans isolated from other proteins) mimicked the effects of the intact Tf molecule on apoptosis. Antibodies specific for the Tf receptor (CD71) did not block the effects of Tf or Tf-Gly on apoptosis. Determination of cytokine mRNA in the course of Fas-mediated apoptosis in the presence of Tf or Tf-Gly showed upregulation of mRNA for Fas ligand and TNF-alpha in CD56(+) and downregulation of these transcripts along with upregulation of mRNA for interleukin-10 in CD3(+) marrow cells. Under these conditions, a distinct increase in Fas-associated phosphatase-1 message was observed in CD3(+) cells that were protected by Tf or Tf-Gly against apoptosis. The in vitro data were confirmed in a murine in vivo model in which pretreatment of mice with Tf protected marrow cells against gamma-irradiation-induced cell death. These data suggest a role for Tf and particularly Tf-Gly in the regulation of programmed cell death, apparently via alterations in cytokine expression, and provide a basis for additional studies on the use of Tf in cytoprotective protocols.
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PMID:Pro-apoptotic and anti-apoptotic effects of transferrin and transferrin-derived glycans on hematopoietic cells and lymphocytes. 1130 Nov 88