Abstract:
:Activation of NF-kappaB is regulated via numerous ubiquitin- and proteasome-mediated steps; an important one is processing of the precursor p105 to the p50 active subunit. The mechanisms involved are largely unknown, because this is an exceptional case where the ubiquitin system does not destroy its substrate completely. Here, we demonstrate that proteasomal processing of p105 requires ubiquitin but not generation of polyubiquitin chains. In vitro, ubiquitin species that cannot polymerize mediate processing. In yeasts that express nonpolymerizable ubiquitins, processing proceeds normally, whereas degradation of substrates that are dependent on polyubiquitination is inhibited. Similar results were obtained in mammalian cells. Interestingly, processing requires multiple monoubiquitinations, because progressive elimination of lysines in p105 is accompanied by gradual inhibition of p50 generation. Finally, the proteasome recognizes the multiply monoubiquitinated p105. These findings suggest that a proteolytic signal can be composed of a cluster of single ubiquitins, not necessarily a chain.
journal_name
Mol Celljournal_title
Molecular cellauthors
Kravtsova-Ivantsiv Y,Cohen S,Ciechanover Adoi
10.1016/j.molcel.2009.01.023subject
Has Abstractpub_date
2009-02-27 00:00:00pages
496-504issue
4eissn
1097-2765issn
1097-4164pii
S1097-2765(09)00067-7journal_volume
33pub_type
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