K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody

Mol Cell. 2010 Aug 13;39(3):477-84. doi: 10.1016/j.molcel.2010.07.001. Epub 2010 Jul 22.


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.

MeSH terms

  • Anaphase-Promoting Complex-Cyclosome
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology*
  • Cell Cycle / physiology*
  • HeLa Cells
  • Humans
  • Protein Processing, Post-Translational / physiology*
  • Ubiquitin / chemistry
  • Ubiquitin / immunology
  • Ubiquitin / metabolism*
  • Ubiquitin-Protein Ligase Complexes / metabolism*
  • Ubiquitination / physiology*


  • Antibodies, Monoclonal
  • Ubiquitin
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome