Two distinct ubiquitin-dependent mechanisms are involved in NF-kappaB p105 proteolysis.
Generation of the p50 subunit of NF-kappaB is a rare case in which the ubiquitin system processes a longer precursor, p105, into a shorter active subunit: in the vast majority of cases, the target protein is completely degraded. The mechanisms involved in this process have remained elusive. It appears that a Gly rich region (GRR) in the middle of the molecule serves as a "processing stop signal", though under certain conditions, such as after stimulation, p105 can be completely degraded. Since NF-kappaB plays critical roles in a broad array of basic cellular processes, it is important to dissect the mechanisms that regulate its proteolysis-both destruction and processing. We have previously shown that signal-induced degradation of p105 requires ubiquitination on multiple lysines. Here we describe a novel region, a Processing Inhibitory Domain-PID, that upon its removal, the molecule is processed in high efficiency, which requires ubiquitination on a single, though non-specific, lysine.
Cohen
Shai
S
Center for Vascular and Tumor Biology, The Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa 31096, Israel. shaico@tx.technion.ac.il
Lahav-Baratz
Shirly
S
Ciechanover
Aaron
A