Journal
EMBO JOURNAL
Volume 25, Issue 9, Pages 1945-1956Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.emboj.7601081
Keywords
20S proteasome; NF-kappa B; p105; processing; ubiquitination
Categories
Funding
- NCI NIH HHS [CA71718] Funding Source: Medline
- NIAID NIH HHS [AI064326, R01 AI064326] Funding Source: Medline
- NIGMS NIH HHS [GM071862, P01 GM071862] Funding Source: Medline
Ask authors/readers for more resources
The NF-kappa B p50 is the N-terminal processed product of the precursor, p105. It has been suggested that p50 is generated not from full-length p105 but cotranslationally from incompletely synthesized molecules by the proteasome. We show that the 20S proteasome endoproteolytically cleaves the fully synthesized p105 and selectively degrades the C-terminus of p105, leading to p50 generation in a ubiquitin-independent manner. As small as 25 residues C-terminus to the site of processing are sufficient to promote processing in vivo. However, any p105 mutant that lacks complete ankyrin repeat domain (ARD) is processed aberrantly, suggesting that native processing must occur from a precursor, which extends beyond the ARD. Remarkably, the mutant p105 that lacks the internal region including the glycine-rich region (GRR) is completely degraded by 20S proteasome in vitro. This suggests that the GRR impedes the complete degradation of the p105 precursor, thus contributing to p50 generation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available