Abstract:
:Polyubiquitination is a posttranslational modification where ubiquitin chains containing isopeptide bonds linking one of seven ubiquitin lysines with the C terminus of an adjoining ubiquitin are covalently attached to proteins. While functions of K48- and K63-linked polyubiquitin are understood, the role(s) of noncanonical K11-linked chains is less clear. A crystal structure of K11-linked diubiquitin demonstrates a distinct conformation from K48- or K63-linked diubiquitin. We engineered a K11 linkage-specific antibody and use it to demonstrate that K11 chains are highly upregulated in mitotic human cells precisely when substrates of the ubiquitin ligase anaphase-promoting complex (APC/C) are degraded. These chains increased with proteasomal inhibition, suggesting they act as degradation signals in vivo. Inhibition of the APC/C strongly impeded the formation of K11-linked chains, suggesting that a single ubiquitin ligase is the major source of mitotic K11-linked chains. Our results underscore the importance of K11-linked ubiquitin chains as critical regulators of mitotic protein degradation.
journal_name
Mol Celljournal_title
Molecular cellauthors
Matsumoto ML,Wickliffe KE,Dong KC,Yu C,Bosanac I,Bustos D,Phu L,Kirkpatrick DS,Hymowitz SG,Rape M,Kelley RF,Dixit VMdoi
10.1016/j.molcel.2010.07.001subject
Has Abstractpub_date
2010-08-13 00:00:00pages
477-84issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(10)00523-Xjournal_volume
39pub_type
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