Recruitment of proteasome catalytic subunit dictates NFkB-mediated transcriptional termination (136.3)

Abstract

Abstract The ubiquitin proteasome pathway plays a vital role in the regulation of transcription. While a biphasic involvement of the proteasome has been demonstrated in the regulation of immune response gene inducer, Nuclear factor Kappa B (NFκB), the precise molecular link between the proteasome and the persistence of NFκB mediated transcription remains to be fully defined. Using pervanadate, a stimulus that induces nuclear NFκB in the absence of proteasomal proteolysis of IκB-α, akin to reactive oxygen species, ChIP analyses and qPCR, we now present evidence that pervanadate in combination with proteasomal inhibition induces exaggerated expression of NFκB-mediated proinflammatory genes. We also report that both the 19S and 20S components of the proteasome complex appear to play distinct but non-redundant roles in the regulation of NFκB mediated transcription. Our results provide insight into the role of proteasomal complexes in NFκB transcriptional regulation and uncover a novel role for the proteasome in chronic inflammatory responses and increased inflammation accompanying aging, This research was supported by grants AG013081 and AG025220 from the NIH.