Regulation of the specific DNA binding activity of Xenopus laevis p53: evidence for conserved regulation through the carboxy-terminus of the protein

Bessard, Anne-Claire Hardy; Garay, Edith; Penard-Lacronique, Virginie; Legros, Yann; Demarquay, Christel; Houque, Armelle; Portefaix, Jean Michel; Granier, Claude; Soussi, Thierry

doi:10.1038/sj.onc.1201598

Cited by 20 publications

(24 citation statements)

References 26 publications

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“…Homology in the amino-terminus is restricted to the mdm2 binding site whereas the homology in the carboxy-terminus is localized in the oligomerization domain. We have produced several panels of mAbs toward human and xenopus p53 (Legros et al, 1994a;Hardy-Bessard et al, 1998). About 60% of these mAbs recognized an immunodominant epitope localized in the amino-terminus of the p53 that contains the binding site of p53 to mdm2 ( Figure 1B).…”

Section: P53 P73 and P63 Cross Reactivitymentioning

confidence: 99%

“…These findings are totally in accordance with the work performed in mice on the production of p53 monoclonal antibodies (mAbs). Immunization of mice with either murine, xenopus or human wild-type p53 led to the production of mAbs directed to linear epitopes localized in the amino-and carboxy-terminus of p53 (Vojtesek et al, 1992;Bartek et al, 1993;Legros et al, 1994a;Hardy-Bessard et al, 1998). MAbs specific for the central region of the protein were obtained only after a special immunization or selection procedure (Legros et al, 1994b;Vojtesek et al, 1995).…”

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confidence: 99%

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Detection of p73 antibodies in patients with various types of cancer: immunological characterization

et al. 2001

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Summary p53 antibodies have been found in the sera of patients with various types of cancer. The presence of these antibodies is generally associated with p53 accumulation in the tumour that is believed to trigger this humoral response. The recent discovery of 2 new members of the p53 family, p73 and p63, led us to study the specificity of this immune response towards the 3 proteins. Serum samples from 148 patients with various types of cancer were tested for antibodies against p73 and p63 using immunoprecipitation. 72 patients were previously shown to have p53 antibodies whereas 76 were negative. The control group consisted of 50 blood donors. p73 were detected in 22/148 (14.9%) of the cancer patients (11/72 in the group with p53-antibodies and 11/76 in the negative group). Only two sera from the control (4%) were positive. p63 antibodies were detected in only 4/148 (2.7%) of the cancer patients. Epitope mappings were performed and demonstrate that p73 antibodies are directed toward the central region of the p73 protein whereas p53 antibodies react predominantly toward the amino-and the carboxy-terminus of p53. Our results indicate that there is a specific immune response toward the p73 protein in cancer patients, a finding supported by an increasing number of publications describing p73 accumulation in tumoral cells.

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Section: P53 P73 and P63 Cross Reactivitymentioning

confidence: 99%

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confidence: 99%

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

et al. 2001

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“…The regulation of p53 via mdm2 protein is also conserved throughout evolution, and it has been shown that xdm2 is able to bind mammalian p53 (Kussie et al, 1996;Marechal et al, 1997). The binding of hdm2 to Xp53 led to inactivation of the transactivational activity of p53 (Hardy-Bessard et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Regulation of the cell cycle by p53 after DNA damage in an amphibian cell line

2001

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In mammalian cells, the p53 protein is a key regulator of the cell cycle following DNA damage. In the present study, we investigated the function of p53 in the A6 amphibian cell line. Using various speci®c Xenopus p53 monoclonal antibodies, we showed that Xenopus p53 accumulates after DNA damage, including gamma and UV irradiation or treatment with adriamycin. Such accumulation is accompanied by an increase in the apparent molecular weight of the protein. This change was shown to be the result of a phosphorylation event that occurs after DNA damage. Accumulation of Xenopus p53 is parallel to a drastic change in the cell cycle distribution. Brief exposure to adriamycin or gamma irradiation induces reversible growth arrest, whereas long-term exposure to adriamycin leads to apoptosis. Taken together, these results indicate that p53 has a similar behaviour in frog cells and mammalian cells, and that it conserves two activities, cell cycle arrest and apoptosis. Oncogene (2001) 20, 3766 ± 3775.

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“…It is generally assumed that this consensus is conserved in the mouse, but no systematic studies have been performed to verify this point. The main argument suggesting that this consensus could be conserved in various species is derived from the finding that X. laevis p53 binds efficiently to this consensus sequence in a similar way to human p53 (Hardy-Bessard et al, 1998). X. laevis p53 also efficiently transactivates human p53 target genes, such as p21WAF1 or bax.…”

Section: The P53 Familymentioning

confidence: 99%

“…This is the first time that p53 RE has been reported in nonmammalian species. Experimental evidence is necessary to demonstrate the biological activity of these sequences, but several lines of experimental evidence already suggest that mammalian and X. laevis p53 are interchangeable and behave in similar ways (Hardy-Bessard et al, 1998;Bensaad et al, 2001).…”

Section: Other P53 Target Genesmentioning

confidence: 99%

Data mining the p53 pathway in the Fugu genome: evidence for strong conservation of the apoptotic pathway

2003

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The p53 tumour suppressor gene belongs to a small family of related proteins that includes two other members, p63 and p73. Phylogenetic and functional studies suggest that p63 and p73 are ancient genes that have essential roles in normal development, whereas p53 seems to have evolved more recently to prevent cell transformation. In mammalian cells, a plethora of proteins have been found to specifically regulate p53 activity. The genome of the fish Fugu rubripes has been recently published. It is the second vertebrate genome for which the entire sequence is now available. Phylogenetic studies are essential in order to analyse and define signalling pathways important for cell cycle regulation. The presence or absence of a critical member in any pathway can shed light about the evolution of these pathways. The Fugu genome databank has been analysed for several members of the p53 network, including p53, p63 and p73. A good conservation of the network that regulates p53 stability and apoptosis has been found. We also discovered that some cofactors that cooperate with p53 for apoptosis are also well conserved and belong to multigene families not detected in the human genome.

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Regulation of the specific DNA binding activity of Xenopus laevis p53: evidence for conserved regulation through the carboxy-terminus of the protein

Cited by 20 publications

References 26 publications

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

Detection of p73 antibodies in patients with various types of cancer: immunological characterization

Regulation of the cell cycle by p53 after DNA damage in an amphibian cell line

Data mining the p53 pathway in the Fugu genome: evidence for strong conservation of the apoptotic pathway

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