Association of protein disulfide isomerase activity and the induction of contact inhibition.
Interferon-beta (IFN-beta) used as a biological response modifier can cause a wide array of effects, including the restoration of contact inhibition in HT1080 fibrosarcoma cells normally lacking this control. Sequence analysis and characterization of a cDNA whose expression has been shown to be transiently induced by IFN-beta now identifies this cDNA as corresponding to the gene for the multifunctional polypeptide protein disulfide isomerase (PDI). Cell proliferation studies using bacitracin as an inhibitor of PDI demonstrated that contact inhibition could be suppressed in human fibroblasts which normally exhibit this control--allowing attainable cell saturation densities to be significantly greater than those of control cells. PDI enzyme activity assays indicated that 1 mM bacitracin inhibited PDI intracellular activity up to 60%. Moreover, evaluations of PDI levels in normal fibroblasts of increasing densities suggested that enzyme levels correlate with density-dependent growth control, showing a transient increase in intracellular activity as cells approach confluency. Together these results suggest that induction of PDI activity is not only involved in the antiproliferative actions of IFN-beta, but it is critical to the regulation of contact inhibition growth control in normal fibroblasts.
Clive
D R
DR
Department of Biology, Catholic University of America, Washington, DC 20064.
Greene
J J
JJ
D001414:Bacitracin / Q000494:pharmacology; D002455:Cell Division; D002478:Cells, Cultured; D003260:Contact Inhibition / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology; D007535:Isomerases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors; D019704:Protein Disulfide-Isomerases; D017422:Sequence Analysis, DNA
D001414:Bacitracin; D016899:Interferon-beta; D011393:Procollagen-Proline Dioxygenase; D007535:Isomerases; D019704:Protein Disulfide-Isomerases