The ubiquitinproteasome pathway is required for processing the NF-κB1 precursor protein and the activation of NF-κB

VJ Palombella, OJ Rando, AL Goldberg, T Maniatis - Cell, 1994 - cell.com
VJ Palombella, OJ Rando, AL Goldberg, T Maniatis
Cell, 1994cell.com
We demonstrate an essential role for the proteasome complex in two proteolytic processes
required for activation of the transcription factor NF-κB. The p105 precursor of the p50
subunit of NF-κB is processed in vitro by an ATP-dependent process that requires
proteasomes and ubiquitin conjugation. The C-terminal region of p105 is rapidly degraded,
leaving the N-terminal p50 domain. p105 processing can be blocked in intact cells with
inhibitors of the proteasome or in yeast with proteasome mutants. These inhibitors also block …
Summary
We demonstrate an essential role for the proteasome complex in two proteolytic processes required for activation of the transcription factor NF-κB. The p105 precursor of the p50 subunit of NF-κB is processed in vitro by an ATP-dependent process that requires proteasomes and ubiquitin conjugation. The C-terminal region of p105 is rapidly degraded, leaving the N-terminal p50 domain. p105 processing can be blocked in intact cells with inhibitors of the proteasome or in yeast with proteasome mutants. These inhibitors also block the activation of NF-κB and the rapid degradation of IκBα induced by tumor necrosis factor α. Thus, the ubiquitinproteasome pathway functions not only in the complete degradation of polypeptides, but also in the regulated processing of precursors into active proteins.
cell.com