Viability and DNA damage responses of TPPII-deficient Myc- and Ras-transformed fibroblasts

Journal Article · Fri Sep 04 00:00:00 EDT 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.06.068· OSTI ID:22199779

Tsurumi, Chizuko; Firat, Elke; Gaedicke, Simone ^[1]; Huai, Jisen ^[2]; Mandal, Pankaj Kumar ^[3]; Niedermann, Gabriele ^[1]

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1. Department of Radiation Oncology, University Hospital Freiburg, Freiburg (Germany)
2. Institute of Molecular Medicine and Cell Research, Center for Biochemistry and Molecular Cell Research, Albert-Ludwig University, Freiburg (Germany)
3. Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Institute of Clinical Molecular Biology and Tumor Genetics, Muenchen (Germany)

Tripeptidyl peptidase II (TPPII) is a giant cytosolic protease. Previous protease inhibitor, overexpression and siRNA studies suggested that TPPII is important for viability and proliferation of tumor cells, and for their ionizing radiation-induced DNA damage response. The possibility that TPPII could be targeted for tumor therapy prompted us to study its role in transformed cells following genetic TPPII deletion. We generated cell lines from primary fibroblasts having conditional (floxed) TPPII alleles, transformed them with both the c-myc and H-ras oncogenes, and deleted TPPII using retroviral self-deleting Cre recombinase. Clonally derived TPPIIflox/flox and TPPII-/- transformed fibroblasts showed no influences of TPPII expression on basal cell survival and proliferation, nor on radiation-induced p53 activation, p21 induction, cell cycle arrest, apoptosis, or clonogenic cell death. Thus, our results do not support a generally important role of TPPII for viability and proliferation of transformed cells or their p53-mediated DNA damage response.

• OSTI ID: 22199779
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 386, Issue 4; Other Information: Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS
APOPTOSIS
CELL CYCLE
DNA DAMAGES
FIBROBLASTS
GAMMA RADIATION
GENETIC RADIATION EFFECTS
IRRADIATION
MONOCLINIC LATTICES
NEOPLASMS
ONCOGENES
THERAPY
TUMOR CELLS
VIABILITY