A minimal glycine-alanine repeat prevents the interaction of ubiquitinated IκBα with the proteasome: a new mechanism for selective inhibition of proteolysis

The Epstein-Barr virus nuclear antigen 1 contains a glycine-alanine repeat that inhibits in cis MHC class l-restricted presentation. We report here that insertion of a minimal glycine-alanine repeat motif in different positions of IκBα protects this NF-κB inhibitor from signal–induced degradation dependent on ubiquitin-proteasome, and decreases its basal turnover in vivo resulting in constitutive dominant-negative mutants. The chimeras are phosphorylated and ubiquitinated in response to tumor necrosis factor α, but are then released from NF-κB and fail to associate with the proteasome. This explains how functionally competent IκBα is protected from proteasomai disruption and identifies the glycine-alanine repeat as a new regulator of proteolysis.

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