Suppression of the transcriptional activity and DNA binding of nuclear factor-kappa B by a paraneoplastic cerebellar degeneration-associated antigen.
Paraneoplastic cerebellar degeneration (PCD) associated with gynecological malignancies is a disorder in which an autoimmune mechanism has been suggested, and both antibody- and cell-mediated immune responses exist against pcd17/cdr2, a neural protein expressed in cerebellar Purkinje neurons and brainstem neurons. In this report, we describe that pcd17 can suppress the basal or activated NF-kappaB-dependent transcriptional activity in a co-transfection study. The DNA binding of constitutive NF-kappaB complexes decreased in the nucleus of TNF-alpha-stimulated neuroblastoma cells, though pcd17 does not bind to classical NF-kappaB consensus site. These data indicate that pcd17 is a potential repressor for NF-kappaB-dependent gene transcription in neurons.
Sakai
K
K
Department of Neurology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Kahoku-gun, Ishikawa 920-0293, Japan. ksakai@kanazawa-med.ac.jp
Kitagawa
Y
Y
Li
Y
Y
Shirakawa
T
T
Hirose
G
G
D000818:Animals; D019556:COS Cells; D002526:Cerebellar Diseases / Q000276:immunology; D004247:DNA / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D009410:Nerve Degeneration / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D010257:Paraneoplastic Syndromes / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C095184:CDR2 protein, human; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA