The Aryl Hydrocarbon Nuclear Translocator Alters Cd30-Mediated Nf-Kappa B-Dependent Transcription

Expression and signaling of CD30, a tumor necrosis factor receptor family member, is up- regulated in numerous lymphoid- derived neoplasias, most notably anaplastic large- cell lymphoma ( ALCL) and Hodgkin's lymphoma. To gain insight into the mechanism of CD30 signaling, we used an affinity purification strategy that led to the identification of the aryl hydrocarbon receptor nuclear translocator ( ARNT) as a CD30- interacting protein that modulated the activity of the RelB subunit of the transcription factor nuclear factor kappa B (NF-kappa B). ALCL cells that were deficient in ARNT exhibited defects in RelB recruitment to NF-kappa B-responsive promoters, whereas RelA recruitment to the same sites was potentiated, resulting in the augmented expression of these NF-kappa B-responsive genes. These findings indicate that ARNT functions in concert with RelB in a CD30- induced negative feedback mechanism.