Abstract：
:Protein ubiquitination regulates many cellular processes, including protein degradation, signal transduction, DNA repair and cell division. In the classical model, a uniform polyubiquitin chain that is linked through Lys 48 is required for recognition and degradation by the 26S proteasome. Here, we used a reconstituted system and quantitative mass spectrometry to demonstrate that cyclin B1 is modified by ubiquitin chains of complex topology, rather than by homogeneous Lys 48-linked chains. The anaphase-promoting complex was found to attach monoubiquitin to multiple lysine residues on cyclin B1, followed by poly-ubiquitin chain extensions linked through multiple lysine residues of ubiquitin (Lys 63, Lys 11 and Lys 48). These heterogeneous ubiquitin chains were sufficient for binding to ubiquitin receptors, as well as for degradation by the 26S proteasome, even when they were synthesized with mutant ubiquitin that lacked Lys 48. Together, our observations expand the context of what can be considered to be a sufficient degradation signal and provide unique insights into the mechanisms of substrate ubiquitination.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Kirkpatrick DS,Hathaway NA,Hanna J,Elsasser S,Rush J,Finley D,King RW,Gygi SPdoi
10.1038/ncb1436subject
Has Abstractpub_date
2006-07-01 00:00:00pages
700-10issue
7eissn
1465-7392issn
1476-4679pii
ncb1436journal_volume
8pub_type
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