The aryl hydrocarbon nuclear translocator alters CD30-mediated NF-kappaB-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 kappaB (NF-kappaB). ALCL cells that were deficient in ARNT exhibited defects in RelB recruitment to NF-kappaB-responsive promoters, whereas RelA recruitment to the same sites was potentiated, resulting in the augmented expression of these NF-kappaB-responsive genes. These findings indicate that ARNT functions in concert with RelB in a CD30-induced negative feedback mechanism.
Wright
Casey W
CW
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Duckett
Colin S
CS
D000595:Amino Acid Sequence; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D004247:DNA / Q000378:metabolism; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
C497396:ARNT protein, human; D017730:Ki-1 Antigen; D016328:NF-kappa B; C497593:RELB protein, human; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051841:Transcription Factor RelB; D004247:DNA