An isoform of protein disulfide isomerase isolated from chronic myelogenous leukemia cells alters complex formation between nuclear proteins and regulatory regions of interferon-inducible genes.
We have previously shown that the electrophoretic mobility of complexes formed in vitro between nuclear proteins and the regulatory domains of interferon-inducible genes is altered by an extranuclear protein present in elevated levels in the myeloid cells of chronic myelogenous leukemia patients. Interferon-alpha reduces the level of this activity only in the cells of patients who are clinically sensitive to the antiproliferative effects of interferon-alpha. We have purified this protein to homogeneity and found it to be a 57-kDa protein which corresponds to an isoform of protein disulfide isomerase. Protein disulfide isomerase is an oxidoreductase which catalyzes the interconversion between the reduced and oxidized states of proteins which contain multiple sulfhydryl groups and disulfide bonds. These studies suggest that this protein may play an important role in the transcriptional activation of interferon-inducible genes, perhaps through redox mechanisms.
Johnson
E
E
Department of Hematology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Henzel
W
W
Deisseroth
A
A
D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D002846:Chromatography, Affinity; D002852:Chromatography, Ion Exchange; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D007535:Isomerases / Q000302:isolation & purification / Q000378:metabolism*; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D015345:Oligonucleotide Probes; D019704:Protein Disulfide-Isomerases; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured
D016898:Interferon-alpha; D007527:Isoenzymes; D009687:Nuclear Proteins; D015345:Oligonucleotide Probes; D007535:Isomerases; D019704:Protein Disulfide-Isomerases