This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wesierska-Gadek, J. Articles by Schmid, G. Search for Related Content PubMed PubMed Citation Articles by Wesierska-Gadek, J. Articles by Schmid, G.

Reduced Stability of Regularly Spliced but not Alternatively Spliced p53 Protein in PARP-deficient Mouse Fibroblasts¹

Józefa Wsierska-Gdek², Zhao-Qi Wang and Gerald Schmid

Institute of Tumorbiology-Cancer Research, University of Vienna, A-1090 Vienna, Austria [J. W-G., G. S.]; and International Agency for Research on Cancer, 69372 Lyon, France [Z-Q. W.]

The interaction between poly(ADP-ribose) polymerase (PARP) and the product of the tumor suppressor gene p53 has been described previously. Here, we have investigated whether PARP deficiency may affect the expression and regulation of wild-type (wt) p53. For this purpose, we have used immortalized cells derived from wt and PARP knockout mice. We have found a clearly reduced basal level of PAb421 immunoreactive wt p53 protein in PARP-deficient cells. The monoclonal antibody PAb421 is known to recognize an epitope in the COOH terminus of normally spliced p53 protein. Under indirect immunofluorescence, this antibody stained nuclei in normal but not in PARP-deficient cells. Despite marked reduction of wt p53 protein in PARP knockout cells, no significant difference of the p53 transcription rate was observed between wt and PARP-deficient cells. Interestingly, in both cell types, an additional p53 transcript representing the alternatively spliced (AS) p53 form was detected. Because of its reactivity with different specific anti-p53 antibodies, we have determined that the p53 protein present in PARP knockout mouse cells possesses characteristic features of AS p53. Our results clearly show that PARP-deficient cells constitutively express the AS form of wt p53 and indicate that the regularly spliced p53 is extremely unstable in the absence of PARP. Moreover, PARP-/- cells fail to transactivate p53-responsive genes. Treatment of PARP-/- cells with genotoxic agents primarily leads to the activation of AS p53 protein.

This article has been cited by other articles:

				C. Baumann, G. S. Boehden, A. Burkle, and L. Wiesmuller Poly(ADP-RIBOSE) polymerase-1 (Parp-1) antagonizes topoisomerase I-dependent recombination stimulation by P53 Nucleic Acids Res., February 9, 2006; 34(3): 1036 - 1049. [Abstract] [Full Text] [PDF]

				J. Wesierska-Gadek, D. Schloffer, M. Gueorguieva, M. Uhl, and A. Skladanowski Increased Susceptibility of Poly(ADP-Ribose) Polymerase-1 Knockout Cells to Antitumor Triazoloacridone C-1305 Is Associated with Permanent G2 Cell Cycle Arrest Cancer Res., July 1, 2004; 64(13): 4487 - 4497. [Abstract] [Full Text] [PDF]

				S. Ishizuka, K. Martin, C. Booth, C. S. Potten, G. de Murcia, A. Burkle, and T. B. L. Kirkwood Poly(ADP-ribose) polymerase-1 is a survival factor for radiation-exposed intestinal epithelial stem cells in vivo Nucleic Acids Res., November 1, 2003; 31(21): 6198 - 6205. [Abstract] [Full Text] [PDF]

				S. Wieler, J.-P. Gagne, H. Vaziri, G. G. Poirier, and S. Benchimol Poly(ADP-ribose) Polymerase-1 Is a Positive Regulator of the p53-mediated G1 Arrest Response following Ionizing Radiation J. Biol. Chem., May 23, 2003; 278(21): 18914 - 18921. [Abstract] [Full Text] [PDF]

				H. Lovborg, J. Wojciechowski, R. Larsson, and J. Wesierska-Gadek Action of a Novel Anticancer Agent, CHS 828, on Mouse Fibroblasts: Increased Sensitivity of Cells Lacking Poly (ADP-Ribose) Polymerase-1 Cancer Res., August 1, 2002; 62(15): 4206 - 4211. [Abstract] [Full Text] [PDF]

				X. Wang, D. Michael, G. de Murcia, and M. Oren p53 Activation by Nitric Oxide Involves Down-regulation of Mdm2 J. Biol. Chem., May 3, 2002; 277(18): 15697 - 15702. [Abstract] [Full Text] [PDF]

				W.-M. Tong, M. P. Hande, P. M. Lansdorp, and Z.-Q. Wang DNA Strand Break-Sensing Molecule Poly(ADP-Ribose) Polymerase Cooperates with p53 in Telomere Function, Chromosome Stability, and Tumor Suppression Mol. Cell. Biol., June 15, 2001; 21(12): 4046 - 4054. [Abstract] [Full Text]

				M Horky, G Wurzer, V Kotala, M Anton, B Vojtesek, J Vacha, and J Wesierska-Gadek Segregation of nucleolar components coincides with caspase-3 activation in cisplatin-treated HeLa cells J. Cell Sci., January 2, 2001; 114(4): 663 - 670. [Abstract] [PDF]

				G. Wurzer, Z. Herceg, and J. Wsierska-Gadek Increased Resistance to Anticancer Therapy of Mouse Cells Lacking the Poly(ADP-ribose) Polymerase Attributable to Up-Regulation of the Multidrug Resistance Gene Product P-Glycoprotein Cancer Res., August 1, 2000; 60(15): 4238 - 4244. [Abstract] [Full Text]

				W.-M. TONG, D. GALENDO, and Z.-Q. WANG Role of DNA Break-sensing Molecule Poly(ADP-ribose) Polymerase (PARP) in Cellular Function and Radiation Toxicity Cold Spring Harb Symp Quant Biol, January 1, 2000; 65(0): 583 - 592. [Abstract] [PDF]