Abnormality of Oct-1 DNA binding in T cells from Sjögren's syndrome patients.
Primary Sjögren's syndrome (SS) is an autoimmune rheumatic disease characterized by T cell hypoactivity. To understand the diminished T cell response to activation signals, we measured nucleoprotein DNA-binding activities regulating gene expression during T cell activation using the electrophoretic mobility shift assay. Peripheral blood lymphocytes from 9/19 SS patients were found to be defective in their ability to bind an october sequence (Oct-1). This Oct-1-binding phenotype remained stable in culture for up to 3 days prior to activation. This abnormality was not seen in resting T cells nor T cells from patients with systemic lupus erythematosus, rheumatoid arthritis (RA), or SS accompanied by RA. The SS Oct-1 DNA-binding abnormality correlated significantly with an inability of cells to exit the Gzero/G1 cell cycle phase when stimulated in vitro. Importantly, nucleoprotein extracts showing decreased DNA-binding activity had normal amounts of Oct-1 proteins as determined by immunoprecipitation, implying a functional defect in the Oct-1 protein. Moreover, defective DNA binding was corrected by treatment with acid phosphatase.
Flescher
E
E
University of Texas Health Science Center, Audie L. Murphy Memorial Veterans Hospital, San Antonio, USA. flescher@charlotte.med.nyu.edu
Vela-Roch
N
N
Ogawa
N
N
Nakabayashi
T
T
Escalante
A
A
Anaya
J M
JM
Dang
H
H
Talal
N
N
D000328:Adult; D000368:Aged; D001483:Base Sequence; D002352:Carrier Proteins / Q000032:analysis; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D051863:Host Cell Factor C1; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D050811:Octamer Transcription Factor-1; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D012859:Sjogren's Syndrome / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C497692:HCFC1 protein, human; D018398:Homeodomain Proteins; D051863:Host Cell Factor C1; D007376:Interleukin-2; D050811:Octamer Transcription Factor-1; C494165:POU2F1 protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D004247:DNA