Restoration of transcriptional activity of p53 mutants in human tumour cells by intracellular expression of anti-p53 single chain Fv fragments
- 14 January 1999
- journal article
- research article
- Published by Springer Nature in Oncogene
- Vol. 18 (2) , 551-557
- https://doi.org/10.1038/sj.onc.1202338
Abstract
We report here the production and the properties of single chain Fv fragments (scFvs) derived from the anti-p53 monoclonal antibodies PAb421 and 11D3. 11D3 is a newly generated monoclonal antibody which exhibits properties very comparable to those of PAb421. The scFvs PAb421 and 11D3 are able to stably associate with p53 and to restore the DNA binding activity of some p53 mutants in vitro. When expressed in p53−/− human tumour cells, the scFv421 is essentially localized in the cytoplasm in the absence of p53, and in the nucleus when exogenous p53 is present. Thus, p53 is also able to stably associate with an anti-p53 scFv in cells. Cotransfection of p53−/− human tumour cells with expression vectors encoding the His273 p53 mutant and either scFv leads to restoration of the p53 mutant deficient transcriptional activity. These data demonstrate that, in human tumour cells, these scFvs are able to restore a function essential for the tumour suppressor activity of p53 and may represent a novel class of molecules for p53-based cancer therapy.Keywords
This publication has 44 references indexed in Scilit:
- Intrabodies: turning the humoral immune system outside in for intracellular immunizationGene Therapy, 1997
- Induction of the growth inhibitor IGF-binding protein 3 by p53Nature, 1995
- Allosteric activation of latent p53 tetramersCurrent Biology, 1994
- p53-Dependent apoptosis in the absence of transcriptional activation of p53-target genesNature, 1994
- Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein.Genes & Development, 1994
- Differential induction of transcriptionally active p53 following UV or lonizing radiation: Defects in chromosome instability syndromes?Cell, 1993
- WAF1, a potential mediator of p53 tumor suppressionCell, 1993
- Thymocyte apoptosis induced by p53-dependent and independent pathwaysNature, 1993
- p53 is required for radiation-induced apoptosis in mouse thymocytesNature, 1993
- Regulation of the specific DNA binding function of p53Cell, 1992