K11-Linked Polyubiquitination in Cell Cycle Control Revealed by a K11 Linkage-Specific Antibody
2010; Elsevier BV; Volume: 39; Issue: 3 Linguagem: Inglês
10.1016/j.molcel.2010.07.001
ISSN1097-4164
AutoresM Matsumoto, Katherine E. Wickliffe, Ken C. Dong, Christine Yu, Ivan Bosanac, Daisy Bustos, Lilian Phu, Donald S. Kirkpatrick, S.G. Hymowitz, Michael Rapé, Robert F. Kelley, Vishva M. Dixit,
Tópico(s)Cancer-related Molecular Pathways
ResumoPolyubiquitination 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.
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