Mitotic infidelity and centrosome duplication errors in cells overexpressing tripeptidyl-peptidase II.
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.
Stavropoulou
Vaia
V
Microbiology and Tumor Biology Centre, Karolinska Institutet, Stockholm, Sweden.
Xie
Jianjun
J
Henriksson
Marie
M
Tomkinson
Birgitta
B
Imreh
Stefan
S
Masucci
Maria G
MG
D000626:Aminopeptidases; D017209:Apoptosis / Q000502:physiology; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism / Q000502:physiology*; D043171:Chromosomal Instability; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D015854:Up-Regulation
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases