Single chain antibody against the common epitope of mutant p53 restores wild-type activity to mutant p53 protein
Autor: | Gerald Cohen, Naomi Goldfinger, Varda Rotter, Sara Orgad, Beka Solomon |
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Rok vydání: | 2005 |
Předmět: |
p53
Transcription Genetic Mutant Biophysics Down-Regulation Apoptosis Biology medicine.disease_cause Transfection Biochemistry Activity restoration Epitope Single chain Fv fragment Antibodies Mice Protein structure Downregulation and upregulation Structural Biology Genetics medicine Animals Humans Molecular Biology Mutation Immunodominant Epitopes Wild type Cell Biology Molecular biology Protein Structure Tertiary p53-R175H mutant biology.protein Antibody Tumor Suppressor Protein p53 |
Zdroj: | FEBS letters. 579(25) |
ISSN: | 0014-5793 |
Popis: | Here, we describe the biological activity of ME1, a mouse single chain Fv fragment (scFv) against the common epitope of mutant p53, which is efficiently expressed in mammalian cells. We found that in vivo interaction of the conformational p53 mutant R175H protein with the scFv resulted in the acquisition of wild-type p53 characteristics, manifested in trans-activation of p21, as well as induction of apoptosis. Moreover, antibody binding leads to abrogation of the mutant p53 mediated “gain of function” as estimated by downregulation of EGR-1, a transcriptional target of mutant p53. These findings suggest that the scFv restores wild-type properties to mutant p53. |
Databáze: | OpenAIRE |
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