Nonproteolytic functions of ubiquitin in cell signaling

Mol Cell. 2009 Feb 13;33(3):275-86. doi: 10.1016/j.molcel.2009.01.014.


The small protein ubiquitin is a central regulator of a cell's life and death. Ubiquitin is best known for targeting protein destruction by the 26S proteasome. In the past few years, however, nonproteolytic functions of ubiquitin have been uncovered at a rapid pace. These functions include membrane trafficking, protein kinase activation, DNA repair, and chromatin dynamics. A common mechanism underlying these functions is that ubiquitin, or polyubiquitin chains, serves as a signal to recruit proteins harboring ubiquitin-binding domains, thereby bringing together ubiquitinated proteins and ubiquitin receptors to execute specific biological functions. Recent advances in understanding ubiquitination in protein kinase activation and DNA repair are discussed to illustrate the nonproteolytic functions of ubiquitin in cell signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Binding Sites
  • DNA Damage
  • DNA Repair
  • Models, Biological
  • Polyubiquitin / metabolism
  • Protein Transport
  • Signal Transduction*
  • Ubiquitin / metabolism*


  • Ubiquitin
  • Polyubiquitin