Effects of tiazofurin on guanine nucleotide binding regulatory proteins in HL-60 cells.

@article{Kharbanda1990EffectsOT,
  title={Effects of tiazofurin on guanine nucleotide binding regulatory proteins in HL-60 cells.},
  author={Surender M. Kharbanda and Matthew L. Sherman and Donald W Kufe},
  journal={Blood},
  year={1990},
  volume={75 3},
  pages={
          583-8
        }
}
Guanine nucleotide binding proteins (G proteins) are regulatory molecules that couple membrane receptors to effector systems such as adenylate cyclase and phospholipase C. The alpha subunits of G proteins bind to guanosine 5'-diphosphate (GDP) in the unstimulated state and guanosine 5' triphosphate (GTP) in the active state. Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide), a specific inhibitor of inosine monophosphate (IMP) dehydrogenase, decreases guanylate synthesis from IMP in HL… Expand
Inosine monophosphate dehydrogenase inhibitors. Probes for investigations of the functions of guanine nucleotide binding proteins in intact cells.
Taken together, the above reports indicate that the IMP dehydrogenase inhibitors are valuable probes for investigation of the biological functions of guanine nucleotides in intact cells. While theseExpand
Differentiation and Reduction of Intracellular GTP Levels in Hl-60 and U937 Cells Upon Treatment with IMP Dehydrogenase Inhibitors
TLDR
Substantial decreases in type II IMP dehydrogenase and the level of guanine nucleotide, especially GTP, are shown to be associated with cell maturation in a variety of human leukemic cells. Expand
Functionally nonequivalent interactions of guanosine 5'-triphosphate, inosine 5'-triphosphate, and xanthosine 5'-triphosphate with the retinal G-protein, transducin, and with Gi-proteins in HL-60 leukemia cell membranes.
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The hypothesis is put forward that GTP, ITP, and XTP act as differential signal amplifiers and signal sorters at the G-protein level and that chemoattractants stimulate GTP and ITP hydrolysis by Gi-proteins in a receptor-specific manner. Expand
A decrease in the intracellular guanosine 5'-triphosphate concentration is necessary for granulocytic differentiation of HL-60 cells, but growth cessation and differentiation are not associated with a change in the activation state of Ras, the transforming principle of HL-60 cells.
TLDR
A decrease in the intracellular GTP concentration is necessary for HL-60 cells to undergo granulocytic differentiation; and although a high degree of Ras activation contributes to the malignant phenotype of the cell, there is no change in the activation state of Ras during granulocytes differentiation. Expand
Crystal structure of human type II inosine monophosphate dehydrogenase: implications for ligand binding and drug design.
TLDR
The 2.9-A structure of a ternary complex of the human type II isoform of IMPDH is presented, suggesting strategies for the design of isoform-specific agents in antitumor and immunosuppressive drug design. Expand
Inosine-5'-monophosphate dehydrogenase is a rate-determining factor for p53-dependent growth regulation.
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Findings indicate that under physiological conditions IMPD is a rate-determining factor for p53-dependent growth regulation, and suggest that the impd gene may be epistatic to bax and waf1 in growth suppression. Expand
Induction of apoptosis in IL-3-dependent hematopoietic cell lines by guanine nucleotide depletion.
TLDR
Induction of apoptosis by mycophenolic acid (MPA), a specific IMPDH inhibitor, in interleukin-3 (IL-3)-dependent murine hematopoietic cell lines is examined, suggesting their usefulness in chemotherapeutic regimens for hematologic malignancies. Expand
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TLDR
The design and discovery of structurally novel hIMPDH2 inhibitors as potential anticancer agents are reported and provided a guide for further research on the development of safe and effective antic cancer agents, especially against glioblastoma. Expand
Induction of HL60 cell differentiation by tiazofurin and its analogues: characterization and efficacy.
TLDR
Tiazofurin was found to induce expression of a phosphatidylinositol-specific phospholipase C-sensitive Fc gamma-receptor III (FcRIII) on HL60 cells, a feature consistent with neutrophilic, but not monocytic, differentiation. Expand
Gs alpha availability to cholera toxin-catalysed ADP-ribosylation is decreased in membranes of retinoic acid-treated leukemic cell lines HL-60 and THP-1. A posttranslational effect.
TLDR
It is demonstrated that addition of RA to two human myeloid leukemia cell lines, HL-60 and THP-1, does not induce a reduction of the 2 subunit of Gs (Gs alpha) RNA or Gs alpha protein in the plasma membrane but leads to a rapid decrease in the cholera toxin (CTX)-catalysed ADP-ribosylation ofGs alpha. Expand
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