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

doi:10.1016/S0092-8674(94)90482-0

Cell

Volume 78, Issue 5, 9 September 1994, Pages 773-785

https://doi.org/10.1016/S0092-8674(94)90482-0 Get rights and content

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.

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Cell

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

Summary

Biochim. Biophys. Acta

Cell

J. Biol. Chem.

J. Biol. Chem.

Cell

Cell

Int. Rev. Cytol.

J. Biol. Chem.

Cell

Cell

Cell

Curr. Opin. Cell Biol.

Cell

J. Biol. Chem.

Cell

Cell

Cell

Cell

Cell

Cell

Cell

IκB: a specific inhibitor of the NF-κB transcription factor

Science

A 65-kD subunit of active NF-κB is required for inhibition of NF-κB by IκB

Genes Dev.

The IκB proteins: multifunctional regulators of rel/NF-κB transcription factors

Genes Dev.

Tumor necrosis factor and interleukin-1 lead to phosphorylation and loss of IκBα: a mechanism for NF-κB activation

Mol. Cell. Biol.

Cytoplasmic retention, DNA binding and processing of the NF-κB p50 precursor are controlled by a small region in its C-terminus

EMBO J.

Interferon γ stimulation modulates the proteolytic activity and cleavage site preference of 20S mouse proteasomes

J. Exp. Med.

Cloning of a mitogen-inducible gene encoding a κB DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs

Nature

Mutual regulation of the transcriptional activator NF-κB and its inhibitor IκB-α

p105, the NF-κB p50 precursor protein, is one of the cellular proteins complexed with the v-Rel oncoprotein in transformed chicken spleen cells

J. Virol.

A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein

Science

Isolation and characterization of a mammalian gene encoding a high-affinity cAMP phosphodiesterase

Endothelial nuclear factor-κB and the initiation of the atherosclerotic lesion

Lab. Invest.

A single cDNA, hTF∥A/α, encodes both the p35 and p19 subunits of human TF∥A

Genes Dev.

ATP-dependent incorporation of 20S protease into the 26S complex that degrades proteins conjugated to ubiquitin

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