Cellular Homeostasis or Tumorigenesis: USP7 Playing the Double Agent

Abstract

The ubiquitin specific protease USP7/HAUSP is a major deubiquitinase that acts upon a wide spectrum of substrate proteins. Deubiquitination by USP7 generally leads to stabilization of substrates and their rescue from proteasomal degradation, but can also lead to alteration in their intracellular localization and activity. On the basis of its substrate proteins, USP7 has been shown to regulate processes involved in both the maintenance of homeostasis and the promotion of tumorigenesis. USP7, so far does not seem to be a dedicated regulator for either of these cellular phenomena, instead the relative abundance of a particular set of substrates over another being the factor that decides towards which phenomena it will be monopolized. The onset of cancer unfortunately creates an abundance of pro-oncogenic substrates, and this leads to a drastic monopolization of USP7 function towards the enhancement of further pro-oncogenic signaling.