Single chain antibody against the common epitope of mutant p53 restores wild-type activity to mutant p53 protein

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 acquis...

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Bibliographic Details
Published in:FEBS letters 2005-10, Vol.579 (25), p.5609-5615
Main Authors: Orgad, Sara, Goldfinger, Naomi, Cohen, Gerald, Rotter, Varda, Solomon, Beka
Format: Article
Language:English
Subjects:
Activity restoration
Animals
Antibodies - genetics
Antibodies - immunology
Apoptosis
Down-Regulation
Humans
Immunodominant Epitopes - immunology
Mice
Mutation
p53
p53-R175H mutant
Protein Structure, Tertiary - genetics
Single chain Fv fragment
Transcription, Genetic
Transfection
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - immunology
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/j.febslet.2005.09.031