Mechanism of direct degradation of IκBα by 20S proteasome
- 8 August 2005
- journal article
- Published by Wiley in FEBS Letters
- Vol. 579 (21) , 4797-4802
- https://doi.org/10.1016/j.febslet.2005.07.060
Abstract
IκBα regulates activation of the transcription factor NF‐κB. NF‐κB is activated in response to several stimuli, i.e. proinflamatory cytokines, infections, and physical stress. This signal dependent pathway involves IκBα phosphorylation, ubiquitylation, and degradation by 26S proteasome. A signal independent (basal) turnover of IκBα has also been described. Here, we show that IκBα can be directly degraded by 20S proteasomes. Deletion constructs of IκBα allow us to the determine that N‐terminal (ΔN 1–70) and C‐terminal regions (ΔC 280–327, removing the PEST region) of IκBα are not required for IκBα degradation, while a further C‐terminal deletion including part of the arm repeats (ΔC2 245–327) almost completely suppress the degradation by 20S proteasome. Binding and competition experiments demonstrate that the degradation of IκBα involves specific interactions with α2(C3) subunit of the proteasome. Finally, p65/relA (not itself a substrate for 20S proteasome) inhibits the degradation of IκBα by the proteasome. These results recapitulate in vitro the main characteristics of signal independent (basal) turnover of IκBα demonstrated in intact cells.Keywords
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