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Detection of Protein Ubiquitination
09:00

Detection of Protein Ubiquitination

Published on: August 19, 2009

NEDD8 links cullin-RING ubiquitin ligase function to the p97 pathway

Willem den Besten1, Rati Verma, Gary Kleiger

  • 1Division of Biology, California Institute of Technology, Pasadena, California, USA.

Nature Structural & Molecular Biology
|April 3, 2012
PubMed

Insights

The AAA+ ATPase p97 pathway interacts with cullin-RING ubiquitin ligases (CRLs) via the UBXD7 cofactor. This interaction, mediated by a UIM, links CRL function to p97-mediated protein degradation.

Area of Science:

  • Molecular Biology
  • Protein Degradation Pathways
  • Ubiquitin Signaling

Background:

  • AAA+ ATPase p97 and its cofactors are implicated in protein degradation.
  • The precise targets and functions of many p97 cofactors remain unclear.
  • The p97 pathway has been previously linked to cullin-RING ubiquitin ligases (CRLs).

Purpose of the Study:

  • To elucidate the function of the p97 cofactor UBXD7.
  • To investigate the mechanism linking the p97 pathway to CRLs.
  • To identify the role of UBXD7 in mediating interactions between p97 and CRLs.

Main Methods:

  • Investigated the interaction between human UBXD7 and the p97-CRL complex.
  • Utilized yeast ortholog Ubx5 to study cofactor function.
  • Disrupted the ubiquitin-interacting motif (UIM) of Ubx5 to assess CRL binding and substrate degradation.

Main Results:

  • UBXD7 mediates the p97-CRL interaction through its UIM.
  • UBXD7 and Ubx5 bind to the active, NEDD8- or Rub1-modified form of cullins.
  • Disruption of the Ubx5 UIM impairs CRL binding and Cul3 substrate degradation.

Conclusions:

  • UBXD7 is a conserved p97 cofactor that links the p97 pathway to CRLs.
  • The UIM of UBXD7 is crucial for CRL interaction and subsequent substrate degradation.
  • NEDD8 modification of cullins plays a conserved role in connecting CRLs to the p97 degradation machinery.

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