Peptide aptamers targeting mutant p53 induce apoptosis in tumor cells.
Mutations in the p53 tumor suppressor gene frequently result in expression of p53 point mutants that accumulate in cancer cells and actively collaborate with tumor progression through the acquisition of novel properties. Interfering with mutant p53 functions may represent a valid alternative for blocking tumor growth and development of aggressive phenotypes. The interactions and activities of selected proteins can be specifically modulated by the binding of peptide aptamers (PA). In the present work, we isolated PAs able to interact more efficiently with p53 conformational mutants compared with wild-type p53. The interaction between mutant p53 and PAs was further characterized using molecular modeling. Transient expression of PAs was able to reduce the transactivation activity of mutant p53 and to induce apoptosis specifically in cells expressing mutant p53. These PAs could provide a potential strategy to inhibit the oncogenic functions of mutant p53 and improve mutant p53-targeted cancer therapies.
Guida
Elisa
E
The National Laboratory CIB, and Dipartimento di Biochimica, Biofisica, e Chimica delle Macromolecole (BBCM), University of Trieste, Italy.
Bisso
Andrea
A
Fenollar-Ferrer
Cristina
C
Napoli
Marco
M
Anselmi
Claudio
C
Girardini
Javier E
JE
Carloni
Paolo
P
Del Sal
Giannino
G
D017209:Apoptosis / Q000187:drug effects*; D052158:Aptamers, Peptide / Q000494:pharmacology*; D015153:Blotting, Western; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases / Q000378:metabolism; D008958:Models, Molecular; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D019151:Peptide Library; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
D052158:Aptamers, Peptide; D019151:Peptide Library; D016159:Tumor Suppressor Protein p53; D008156:Luciferases