Nucleic Acids Research, 2000, Vol. 28, No. 2 513-519
© 2000 Oxford University Press
p73 competes with p53 and attenuates its response in a human ovarian cancer cell line
Molecular Pharmacology Unit, Department of Oncology, Istituto di Ricerche Farmacologiche ‘Mario Negri’, Via Eritrea 62, 20157 Milan, Italy
The transcriptional activity of the p53 tumor suppressor protein is crucial for the regulation of cell growth, apoptosis and tumor progression. The first identified p53 relative, p73, was reported to be monoallelically expressed in normal tissues. In some tumors, loss of heterozygosity was associated with overexpression of the silent allele. Human p73
was transfected into the wild-type p53-expressing human ovarian carcinoma cell line A2780. Unlike human osteosarcoma Saos-2 cells, A2780 cells could tolerate hyperexpression of p73 and clones overexpressing p73 could be isolated. No p53–p73 protein–protein interaction was found in these clones in co-immunoprecipitation experiments. Endogenous p53 transcriptional activity was markedly decreased both when p73 was integrated into the genome and in transient transfections using a reporter plasmid containing the p53 binding site linked to luciferase. Transient transfection of p73 with a mutation in the DNA-binding domain did not show these effects. The competition for p53 DNA binding by p73 was also evident in gel shift experiments. The results suggest that p73 can modulate p53 function by inhibiting its DNA binding and that overexpression of p73 in tumors might be a novel mechanism of inactivation of p53.
* To whom correspondence should be addressed. Tel: +39 02 3901 4473; Fax: +39 02 354 6277; Email: broggini@irfmn.mnegri.it
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. Malaguarnera, V. Vella, G. Pandini, M. Sanfilippo, V. Pezzino, R. Vigneri, and F. Frasca TAp73{alpha} Increases p53 Tumor Suppressor Activity in Thyroid Cancer Cells via the Inhibition of Mdm2-Mediated Degradation Mol. Cancer Res., January 1, 2008; 6(1): 64 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zangrossi, M. Marabese, M. Broggini, R. Giordano, M. D'Erasmo, E. Montelatici, D. Intini, A. Neri, M. Pesce, P. Rebulla, et al. Oct-4 Expression in Adult Human Differentiated Cells Challenges Its Role as a Pure Stem Cell Marker Stem Cells, July 1, 2007; 25(7): 1675 - 1680. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R Malaguarnera, V Vella, R Vigneri, and F Frasca p53 family proteins in thyroid cancer Endocr. Relat. Cancer, March 1, 2007; 14(1): 43 - 60. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Malaguarnera, A. Mandarino, E. Mazzon, V. Vella, P. Gangemi, C. Vancheri, P. Vigneri, A. Aloisi, R. Vigneri, and F. Frasca The p53-homologue p63 may promote thyroid cancer progression Endocr. Relat. Cancer, December 1, 2005; 12(4): 953 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. M. Moll and N. Slade p63 and p73: Roles in Development and Tumor Formation Mol. Cancer Res., July 1, 2004; 2(7): 371 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. M. Chan, W. Y. Siu, A. Lau, and R. Y. C. Poon How Many Mutant p53 Molecules Are Needed To Inactivate a Tetramer? Mol. Cell. Biol., April 15, 2004; 24(8): 3536 - 3551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Frasca, V. Vella, A. Aloisi, A. Mandarino, E. Mazzon, R. Vigneri, and P. Vigneri p73 Tumor-Suppressor Activity Is Impaired in Human Thyroid Cancer Cancer Res., September 15, 2003; 63(18): 5829 - 5837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. J. Freebern, J. L. Smith, S. S. Chaudhry, C. M. Haggerty, and K. Gardner Novel Cell-specific and Dominant Negative Anti-apoptotic Roles of p73 in Transformed Leukemia Cells J. Biol. Chem., January 17, 2003; 278(4): 2249 - 2255. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Davis, Y. Dong, and R. H. Weiss Overexpression of p73 causes apoptosis in vascular smooth muscle cells Am J Physiol Cell Physiol, January 1, 2003; 284(1): C16 - C23. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Meyers, M. W. Wagner, H.-S. Hwang, T. J. Kinsella, and D. A. Boothman Role of the hMLH1 DNA Mismatch Repair Protein in Fluoropyrimidine-mediated Cell Death and Cell Cycle Responses Cancer Res., July 1, 2001; 61(13): 5193 - 5201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Vikhanskaya, S. Marchini, M. Marabese, E. Galliera, and M. Broggini p73{{alpha}} Overexpression Is Associated with Resistance to Treatment with DNA-damaging Agents in a Human Ovarian Cancer Cell Line Cancer Res., February 1, 2001; 61(3): 935 - 938. [Abstract] [Full Text]
|
|
|
|
|
|
X. Q. Wang, W. M. Ongkeko, A. W. S. Lau, K. M. Leung, and R. Y. C. Poon A Possible Role of p73 on the Modulation of p53 Level through MDM2 Cancer Res., February 1, 2001; 61(4): 1598 - 1603. [Abstract] [Full Text]
|
|
|
|
 |
|
 C.-L. Chen, S.-M. Ip, D. Cheng, L.-C. Wong, and H. Y. S. Ngan p73 Gene Expression in Ovarian Cancer Tissues and Cell Lines Clin. Cancer Res., October 1, 2000; 6(10): 3910 - 3915. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Gong, N. Nikrui, D. Chen, S. Koido, Z. Wu, Y. Tanaka, S. Cannistra, D. Avigan, and D. Kufe Fusions of Human Ovarian Carcinoma Cells with Autologous or Allogeneic Dendritic Cells Induce Antitumor Immunity J. Immunol., August 1, 2000; 165(3): 1705 - 1711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Minty, X. Dumont, M. Kaghad, and D. Caput Covalent Modification of p73alpha by SUMO-1. TWO-HYBRID SCREENING WITH p73 IDENTIFIES NOVEL SUMO-1-INTERACTING PROTEINS AND A SUMO-1 INTERACTION MOTIF J. Biol. Chem., November 10, 2000; 275(46): 36316 - 36323. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. T. Warnick, B. Dabbas, C. D. Ford, and K. A. Strait Identification of a p53 Response Element in the Promoter Region of the hMSH2 Gene Required for Expression in A2780 Ovarian Cancer Cells J. Biol. Chem., July 13, 2001; 276(29): 27363 - 27370. [Abstract] [Full Text] [PDF]
|
|