The Enigma of Tripeptidyl-Peptidase II: Dual Roles in Housekeeping
and Stress
Figure 2
Distinct functions for TPPII in the nucleus and cytosol. (a) TPPII contributes to protein turnover in concert with components of the ubiquitin-proteasome pathway and other cytosolic peptidases. The expression and activity of TPPII is influenced by the following. () The cellular recycling of amino acids from protein building blocks, that is, through degradation of proteins by the ubiquitin-proteasome pathway, inhibited recycling leads to increased activity of TPPII [11, 12, 14]. () The external supply of amino acids. Dilution of cell culture medium in PBS increases TPPII levels [25]. () The organismal demand for amino acids. An increased demand, as observed in cachexia also increases TPPII activity [29, 30]. (4) Endogenous demand for amino acids; a factor that potentially increases TPPII; remains to be tested. (b) In response to ROS production and DNA damage, TPPII shifts its localization from cytosolic to nuclear. This may contribute to the DNA damage response and apoptosis triggering, a model that is under debate. The cytosolic-nuclear shift of TPPII may create a link between mitochondrial respiration and DNA damage signaling in the nucleus.
