K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody.
Mol Cell
; 39(3): 477-84, 2010 Aug 13.
Article
en En
| MEDLINE
| ID: mdl-20655260
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.
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1
Banco de datos:
MEDLINE
Asunto principal:
Ciclo Celular
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Procesamiento Proteico-Postraduccional
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Ubiquitina
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Complejos de Ubiquitina-Proteína Ligasa
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Ubiquitinación
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Anticuerpos Monoclonales
Límite:
Humans
Idioma:
En
Año:
2010
Tipo del documento:
Article