Suppression of the transcriptional activity and DNA binding of nuclear factor-kappa B by a paraneoplastic cerebellar degeneration-associated antigen

Abstract 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-κB-dependent transcriptional activity in a co-transfection study. The DNA binding of constitutive NF-κB complexes decreased in the nucleus of TNF-α-stimulated neuroblastoma cells, though pcd17 does not bind to classical NF-κB consensus site. These data indicate that pcd17 is a potential repressor for NF-κB-dependent gene transcription in neurons.