Mitotic infidelity and centrosome duplication errors in cells overexpressing tripeptidyl-peptidase II.

Abstract	The oligopeptidase tripeptidyl-peptidase II (TPP II) is up-regulated Burkitt's lymphoma (BL) cells that overexpress the c-myc proto-oncogene and is required for their growth and survival. Here we show that overexpression of TPP II induces accelerated growth and resistance to apoptosis in human embryonic kidney 293 cells. This correlates with the appearance of multiple chromosomal aberrations, numerical and structural centrosome abnormalities, and multipolar cell divisions. Similar mitotic aberrations were also observed in a panel of BL lines and were suppressed, in parallel with TPP II down-regulation, upon reversion of BL-like characteristics in EBV-immortalized B lymphocytes carrying a tetracycline-regulated c-myc. Functional TPP II knockdown by small interfering RNA expression in BL cells caused the appearance of giant polynucleated cells that failed to complete cell division. Collectively, these data point to a role of TPP II in the regulation of centrosome homeostasis and mitotic fidelity suggesting that this enzyme may be a critical player in the induction and/or maintenance of genetic instability in malignant cells.
Authors	Vaia Stavropoulou, Jianjun Xie, Marie Henriksson, Birgitta Tomkinson, Stefan Imreh, Maria G Masucci
Journal	Cancer research (Cancer Res) Vol. 65 Issue 4 Pg. 1361-8 (Feb 15 2005) ISSN: 0008-5472 [Print] United States
PMID	15735022 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	MAS1 protein, human Proto-Oncogene Mas Proto-Oncogene Proteins c-myc Aminopeptidases Dipeptidyl-Peptidases and Tripeptidyl-Peptidases tripeptidyl-peptidase 2 Serine Endopeptidases
Topics	Aminopeptidases Apoptosis (physiology) Burkitt Lymphoma (enzymology, genetics, pathology) Cell Cycle (physiology) Cell Growth Processes (physiology) Cell Line, Tumor Centrosome (metabolism, physiology) Chromosomal Instability Dipeptidyl-Peptidases and Tripeptidyl-Peptidases Humans Mitosis (physiology) Proto-Oncogene Mas Proto-Oncogene Proteins c-myc (biosynthesis, genetics) Serine Endopeptidases (genetics, physiology) Transfection Up-Regulation

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