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 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.
Orgad
Sara
S
Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Israel. orgad@post.tau.ac.il
Goldfinger
Naomi
N
Cohen
Gerald
G
Rotter
Varda
V
Solomon
Beka
B
D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology*; D017209:Apoptosis; D015536:Down-Regulation; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D051379:Mice; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*
D000906:Antibodies; D016056:Immunodominant Epitopes; D016159:Tumor Suppressor Protein p53