A MINIMAL GLYCINE-ALANINE REPEAT PREVENTS THE INTERACTION OF UBIQUITINATED I-KAPPA-B-ALPHA WITH THE PROTEASOME - A NEW MECHANISM FOR SELECTIVE-INHIBITION OF PROTEOLYSIS

The Epstein-Barr virus nuclear antigen 1 contains a glycine-alanine re peat that inhibits in cis MHC class I-restricted presentation. We repo rt here that insertion of a minimal glycine-alanine repeat motif in di fferent positions of I kappa B alpha protects this NF-kappa B inhibito r from signal-induced degradation dependent on ubiquitin-proteasome, a nd decreases its basal turnover in vivo resulting in constitutive domi nant-negative mutants. The chimeras are phosphorylated and ubiquitinat ed in response to tumor necrosis factor alpha, but are then released f rom NF-kappa B and fail to associate with the proteasome. This explain s how functionally competent I kappa B alpha is protected from proteas omal disruption and identifies the glycine-alanine repeat as a new reg ulator of proteolysis.