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Journal of Oncology
Volume 2010, Article ID 128478, 10 pages
Review Article

The Enigma of Tripeptidyl-Peptidase II: Dual Roles in Housekeeping and Stress

1Center for Molecular Medicine (CMM), Department of Medicine, Karolinska Institute, Karolinska University Hospital, 171 76 Stockholm, Sweden
2Department of Biochemistry and Molecular Biology, University of Ferrara, 44100 Ferrara, Italy

Received 30 November 2009; Revised 25 May 2010; Accepted 12 July 2010

Academic Editor: Bruce Baguley

Copyright © 2010 Giulio Preta et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The tripeptidyl-peptidase II complex consists of repeated 138 kDa subunits, assembled into two twisted strands that form a high molecular weight complex ( 5 MDa). TPPII, like many other cytosolic peptidases, plays a role in the ubiquitin-proteasome pathway downstream of the proteasome as well as in the production and destruction of MHC class I antigens and degradation of neuropeptides. Tripeptidyl-peptidase II activity is increased in cells with an increased demand for protein degradation, but whether degradation of cytosolic peptides is the only cell biological role for TPPII has remained unclear. Recent data indicated that TPPII translocates into the nucleus to control DNA damage responses in malignant cells, supporting that cytosolic “housekeeping peptidases” may have additional roles in cell biology, besides their contribution to protein turnover. Overall, TPPII has an emerging importance in several cancer-related fields, such as metabolism, cell death control, and control of genome integrity; roles that are not understood in detail. The present paper reviews the cell biology of TPPII and discusses distinct roles for TPPII in the nucleus and cytosol.