A minimal glycine-alanine repeat prevents the interaction of ubiquitinated I kappaB alpha with the proteasome: a new mechanism for selective inhibition of proteolysis
- PMID: 9701247
- DOI: 10.1038/nm0898-939
A minimal glycine-alanine repeat prevents the interaction of ubiquitinated I kappaB alpha with the proteasome: a new mechanism for selective inhibition of proteolysis
Abstract
The Epstein-Barr virus nuclear antigen 1 contains a glycine-alanine repeat that inhibits in cis MHC class I-restricted presentation. We report here that insertion of a minimal glycine-alanine repeat motif in different positions of I kappaB alpha protects this NF-kappaB 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 alpha, but are then released from NF-kappaB and fail to associate with the proteasome. This explains how functionally competent I kappaB alpha is protected from proteasomal disruption and identifies the glycine-alanine repeat as a new regulator of proteolysis.
Comment in
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Lessons from an age-old war.Nat Med. 1998 Aug;4(8):887-8. doi: 10.1038/nm0898-887. Nat Med. 1998. PMID: 9701231 No abstract available.
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