• Register
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.


Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.


Polyubiquitin-sensor proteins reveal localization and linkage-type dependence of cellular ubiquitin signaling.

Polyubiquitin chain topology is thought to direct modified substrates to specific fates, but this function-topology relationship is poorly understood, as are the dynamics and subcellular locations of specific polyubiquitin signals. Experimental access to these questions has been limited because linkage-specific inhibitors and in vivo sensors have been unavailable. Here we present a general strategy to track linkage-specific polyubiquitin signals in yeast and mammalian cells, and to probe their functions. We designed several high-affinity Lys63 polyubiquitin-binding proteins and demonstrate their specificity in vitro and in cells. We apply these tools as competitive inhibitors to dissect the polyubiquitin-linkage dependence of NF-κB activation in several cell types, inferring the essential role of Lys63 polyubiquitin for signaling via the IL-1β and TNF-related weak inducer of apoptosis (TWEAK) but not TNF-α receptors. We anticipate live-cell imaging, proteomic and biochemical applications for these tools and extension of the design strategy to other polymeric ubiquitin-like protein modifications.

Pubmed ID: 22306808


  • Sims JJ
  • Scavone F
  • Cooper EM
  • Kane LA
  • Youle RJ
  • Boeke JD
  • Cohen RE


Nature methods

Publication Data

March 29, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: 1R01 GM097452
  • Agency: NCI NIH HHS, Id: P01 CA139980
  • Agency: NIGMS NIH HHS, Id: R01 GM097452
  • Agency: NIGMS NIH HHS, Id: R01 GM097452-01
  • Agency: NIGMS NIH HHS, Id: RC1 GM091424
  • Agency: NIGMS NIH HHS, Id: RC1 GM091424
  • Agency: NIGMS NIH HHS, Id: RC1 GM091424-01
  • Agency: NIGMS NIH HHS, Id: RC1 GM091424-02
  • Agency: NCRR NIH HHS, Id: RR020839
  • Agency: Intramural NIH HHS, Id:

Mesh Terms

  • Animals
  • Binding Sites
  • Humans
  • Molecular Probe Techniques
  • Protein Binding
  • Protein Interaction Mapping
  • Signal Transduction
  • Ubiquitin