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Peroxisomal Import Reduces the Proapoptotic Activity of Deubiquitinating Enzyme USP2

Katharina Reglinski1, Marina Keil1, Sabrina Altendorf1

  • 1Institut für Biochemie und Pathobiochemie, Abteilung Systembiochemie, Ruhr-Universität Bochum, D-44780 Bochum, Germany.

Plos One
|October 21, 2015
PubMed

Insights

Human ubiquitin-specific protease 2 (USP2) isoenzymes promote apoptosis. While they enter peroxisomes, their cytosolic presence is key for this function, with import acting as a regulatory mechanism.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Ubiquitin-specific protease 2 (USP2) is a human deubiquitinating enzyme regulating key cellular processes like proliferation and apoptosis.
  • Alternative splicing generates four USP2 isoenzymes, each possessing a weak peroxisome targeting signal type 1 (PTS1).

Purpose of the Study:

  • To systematically analyze the apoptotic effects and intracellular localization of each USP2 isoenzyme.
  • To investigate the role of peroxisomal import in regulating USP2's proapoptotic activity.

Main Methods:

  • Overexpression of USP2 isoenzymes in human cells.
  • Analysis of intracellular localization using microscopy.
  • Assessment of apoptotic effects.
  • Manipulation of peroxisomal import pathways (blocking import, optimizing PTS1, overexpressing PEX5).

Main Results:

  • All USP2 isoenzymes display proapoptotic activity and are imported into peroxisomes via PEX5.
  • A significant portion of USP2 remains in the cytosol due to weak PTS1 affinity.
  • Blocking peroxisomal import did not abolish USP2's proapoptotic function.
  • Enhanced peroxisomal import reduced the apoptotic rate, indicating a regulatory role.

Conclusions:

  • USP2 performs its critical proapoptotic function primarily in the cytosol.
  • Peroxisomal import of USP2 acts as a regulatory mechanism, controlling cytosolic USP2 activity through spatial separation.
  • This spatial control influences interactions with cytosolic and nuclear targets, modulating apoptosis.

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